DK175916B1 - System and method for the treatment of biological fluids - Google Patents

System and method for the treatment of biological fluids Download PDF

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Publication number
DK175916B1
DK175916B1 DK50593A DK50593A DK175916B1 DK 175916 B1 DK175916 B1 DK 175916B1 DK 50593 A DK50593 A DK 50593A DK 50593 A DK50593 A DK 50593A DK 175916 B1 DK175916 B1 DK 175916B1
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medium
system
characterized
biological fluid
ii
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DK50593A
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Danish (da)
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DK50593A (en
DK50593D0 (en
Inventor
David B Pall
Vlado I Matkovich
Thomas Bormann
Thomas C Gsell
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Pall Corp
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Family has litigation
Priority to US60965490 priority Critical
Priority to US07/609,654 priority patent/US5100564A/en
Priority to US9108316 priority
Priority to PCT/US1991/008316 priority patent/WO1992007656A2/en
Application filed by Pall Corp filed Critical Pall Corp
Publication of DK50593D0 publication Critical patent/DK50593D0/en
Publication of DK50593A publication Critical patent/DK50593A/en
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=24441729&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DK175916(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61JCONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/10Bag-type containers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/0209Multiple bag systems for separating or storing blood components
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/0209Multiple bag systems for separating or storing blood components
    • A61M1/0218Multiple bag systems for separating or storing blood components with filters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/0209Multiple bag systems for separating or storing blood components
    • A61M1/0218Multiple bag systems for separating or storing blood components with filters
    • A61M1/0227Multiple bag systems for separating or storing blood components with filters and means for securing the filter against damage, e.g. during centrifugation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/0209Multiple bag systems for separating or storing blood components
    • A61M1/0231Multiple bag systems for separating or storing blood components with gas separating means, e.g. air outlet through microporous membrane or gas bag
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/029Separating blood components present in distinct layers in a container, not otherwise provided for
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. haemofiltration, diafiltration
    • A61M1/3472Filtering material out of the blood by passing it through a membrane, i.e. haemofiltration, diafiltration with treatment of the filtrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3627Degassing devices; Buffer reservoirs; Drip chambers; Blood filters
    • A61M1/3633Blood component filters, e.g. leukocyte filters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3643Priming, rinsing before or after use
    • A61M1/3644Mode of operation
    • A61M1/3646Expelling the residual body fluid after use, e.g. back to the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3643Priming, rinsing before or after use
    • A61M1/3644Mode of operation
    • A61M1/3652Mode of operation using gas, e.g. air
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/145Ultrafiltration
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/147Microfiltration
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/16Feed pretreatment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D63/00Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/08Flat membrane modules
    • B01D63/087Single membrane modules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3693Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • A61M2202/0415Plasma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • A61M2202/0427Platelets; Thrombocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • A61M2202/0429Red blood cells; Erythrocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • A61M2202/0439White blood cells; Leucocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2206/00Characteristics of a physical parameter; associated device therefor
    • A61M2206/10Flow characteristics
    • A61M2206/12Flow characteristics the flow being spirally in a plane, e.g. against a plane side of a membrane filter element
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2311/00Details relating to membrane separation process operations and control
    • B01D2311/04Specific process operations in the feed stream; Feed pretreatment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B04CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04BCENTRIFUGES
    • B04B5/00Other centrifuges
    • B04B5/04Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0407Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
    • B04B2005/0435Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles with adapters for centrifuge tubes or bags

Description

i DK 175916 B1 in DK 175916 B1

Opfindelsen angår et behandlingssystem for et biologisk fluidum af den art, der er angivet i krav l's indledning, og dette system er ejendommeligt ved det i krav l's kendetegnende del angivne. The invention relates to a processing system for a biological fluid of the kind indicated in the preamble to claim, and this system is characterized in the features of claim l's characterizing part indicated. Foretrukne udførelsesformer for 5 systemet er angivet i krav 2-11. Preferred embodiments of the system 5 are defined in claims 2-11. Opfindelsen angår også en fremgangsmåde til behandling af et biologisk fluidum af den art, der er angivet i krav 12's indledning, hvilken fremgangsmåde er ejendommelig ved det i krav 12's kendetegnende del angivne. The invention also relates to a method for treating a biological fluid of the kind specified in the preamble to claim 12, which process is characterized in that in claim 12 the characterizing part indicated. Foretrukne udførelsesformer for fremgangsmåden 10 er angivet i krav 13-15. Preferred embodiments of the method 10 are defined in claims 13-15. Opfindelsen angår endvidere et biologisk fluidumbehandlingssystem af den art, der er angivet i krav 16's indledning, og systemet er ejendommeligt ved det i krav 16's kendetegnende del angivne. The invention further relates to a biological fluid treatment system of the kind specified in the preamble to claim 16 and the system is characterized in that in claim 16 the characterizing part indicated. Foretrukne udførelsesformer for dette system er angivet i krav 17-25. Preferred embodiments of this system are defined in claims 17-25. Opfin-15 delsen angår tillige en fremgangsmåde til behandling af et biologisk fluidum af den art, der er angivet i krav 26's indledning, hvilken fremgangsmåde er ejendommelig ved det i krav 26's kendetegnende del angivne. 15 period inventors also relates to a method of treating a biological fluid of the kind set forth in the preamble to claim 26, which process is characterized in that in claim 26 the characterizing part indicated. Foretrukne udførelsesformer for fremgangsmåden er angivet i krav 27-32. Preferred embodiments of the method are stated in claims 27-32. Endelig 20 angår opfindelsen en fremgangsmåde til behandling af et biologisk fluidum af den art, der er angivet i krav 33's indledning, hvilken fremgangsmåde er ejendommelig ved det i krav 33's kendetegnende del angivne. 20 Finally, the invention relates to a method for treating a biological fluid of the kind indicated in the preamble to claim 33, which process is characterized in that in claim 33 the characterizing part indicated.

Den foreliggende opfindelse angår således et system 25 /til behandling af fx blod fra donorer med det formål at opnå terapeutisk transfusion af blodbestanddele, og der skal i det følgende især beskrives forbedrede metoder og apparater til ud fra donor-helblodet at fremstille blodplade-rigt plasma (herefter kaldet PRP), pakkede røde blodlegemer (her-* 30 efter kaldet PRC), blodplade-koncentrat (herefter kaldet PC) samt plasma. The present invention thus relates to a system 25 / in the treatment of for example blood from donors with the aim of achieving therapeutic transfusion of blood components, and there will now be particularly described improved methods and apparatus for determining from donor whole blood to prepare platelet-rich plasma (hereinafter PRP), packed red blood cells (including 30 * after called PRC), platelet concentrate (hereinafter PC), and plasma.

Udviklingen af plast-blodopsamlingsposer har lettet adskillelsen af donor-helblod i dettes forskellige bestanddele og analoge produkter, hvorved disse forskellige blod-35 produkter, f.eks. The development of plastic blood collection bags has facilitated the separation of donated whole blood into its various components and analogous products, whereby these different blood products 35, for example. blodplade-koncentrater, gøres tilgængelige som et transfusionsprodukt. platelet concentrates are made available as a transfusion product.

DK 175916 B1 I In DK 175916 B1

I tidens løb og under akkumulering af researchdata I Over time and during accumulation of research data in

og kliniske data er transfusionspraksis i høj grad blevet ændret. and clinical data, transfusion practices greatly changed. Ét aspekt ved den gængse praksis er, at helblod One aspect of current practice is that whole blood

sjældent indgives; rarely administered; i stedet gives der til patienter, der I instead given to patients in

5 har behov for røde blodlegemer, pakkede røde blodlegemer, ' I 5 are in need of red blood cells, packed red blood cells, 'I

patienter, der har behov for blodplader, gives blodplade- I patients in need of platelets, platelet given in

koncentrat, og patienter, der har behov for plasma, gives ” I concentrate, and patients needing plasma are given "In

plasma. plasma. I IN

Af denne grund har adskillelsen af blodet i dets I For this reason, the separation of blood into its I

10 bestanddele en væsentlig terapeutisk og økonomisk værdi. 10 components a substantial therapeutic and monetary value.

Dette er intetsteds mere evident end ved behandlingen af This is nowhere more evident than in the treatment of

den forøgede beskadigelse af en patients immunsystem, der I the increased damage to a patient's immune system, which

forårsages af de højere doser og kraftigere virkende læge- I caused by the higher doses and more potent medical In

midler, der nu anvendes ved kemoterapi af cancerpatienter. agents that are now used in chemotherapy of cancer patients. I IN

15 Disse mere aggressive kemoterapi-behandlinger er direkte I 15 These more aggressive chemotherapy treatments directly in

impliceret i formindskelsen af blodpladeindholdet i blodet til abnormt lave niveauer. implicated in the reduction of the platelet content of the blood to abnormally low levels. Associeret indre og ydre blødning Associated internal and external bleeding

kræver desuden mere hyppige transfusioner af PC, og dette I additionally requires more frequent transfusions of PC, and this I

har lagt pres på blodbanker til forøgelse af blodpladeudbyt- I has put pressure on blood banks to increase blodpladeudbyt- In

20 tet pr. 20 per Tet. enhed af blod. unit of blood. I IN

Ved en typisk blodbestanddel-adskillelsesprocedure, I In a typical blood component separation procedure,

der anvendes i USA, citrat-phosphat-dextrose-adenin (CPDA- I used in the United States, citrate-phosphate-dextrose-adenine (I CPDA-

1)-systemet, benyttes der en række trin til adskillelse af I 1) system, utilizes a series of steps for the separation of I

donorblod i tre bestanddele, idet hver bestanddel har væ- I donated blood into three components, each component having liquid I

25 sentlig terapeutisk og økonomisk værdi. 25 SIGNIFICANT therapeutic and economic value. Ved fremgangsmåden I By the method of

anvendes der typisk en blodopsamlingspose, der er integralt I used is typically a blood collection bag which is integrally I

forbundet via et bøjeligt rør til mindst én, fortrinsvis to I connected via a flexible tube to at least one, preferably two, In

eller flere satellit-poser. or more satellite bags. Ved anvendelse af centrifugering I Using centrifugation in

kan helblod adskilles ved differentiel sedimentering i så- I whole blood may be separated by differential sedimentation in so-I

30 danne værdifulde blodbestanddele som plasma, pakkede røde *, I 30 provide valuable blood components as plasma, packed red *, I

blodlegemer (PRC), blodplader suspenderet i klart plasma j I cells (PRC), platelets suspended in clear plasma j I

(blodplade-rigt plasma eller PRP), blodplade-koncentrat i I (Platelet-rich plasma, or PRP), platelet concentrate in the I

(PC) og cryopræcipitat (der kan kræve ekstra behandling). (PC), and cryoprecipitate (which may require additional treatment). 1 I 1

En typisk procedure til opsamling og behandling af I A typical procedure for the collection and processing of the I

35 helblod kan omfatte følgende: I 35, whole blood may include the following: In

(1) En enhed af donor-helblod (ca. 4 50 ml i praksis I (1) A unit of donated whole blood (about 4 ml of 50 In practice

DK 175916 B1 3 i USA) opsamles fra donorens vene direkte i blodopsamlings-posen, der indeholder CPDA-1 indeholdende næringsstof og anti-koagulationsmiddel. DK 175 916 B1 3 in the United States) is collected from the donor's vein directly into the blood-collecting bag containing CPDA-1 containing the nutrient and anti-coagulant.

(2) Blodopsamlingsposen centrifugeres (centrifugering 5 ved lav hastighed eller "soft-spin"-centrifugering) sammen med dens satellit-poser, hvorved man koncentrerer de røde blodlegemer som PRC i den nedre del af blodopsamlingsposen og i den øvre del af posen efterlader en suspension af PRP. (2) The blood collection bag is centrifuged (spin 5 at low speed, or "soft-spin" centrifugation) together with its satellite bags, thereby concentrating the red cells as PRC in the lower portion of the blood collection bag and in the upper part of the bag, leaving a suspension of PRP.

(3) Blodopsamlingsposen overføres, idet man drager 10 omsorg for ikke at forstyrre grænsefladen mellem det ovenstående .PRP-lag og det sedimenterede PRC-lag, i et organ, der er kendt som en "plasma-ekstraktor". (3) The blood collection bag was transferred, with 10 takes care not to disturb the interface between the above-.PRP layer and the sedimented PRC layer, into a body which is known as a "plasma extractor". Denne plasma-eks-traktor eller -ekspressor omfatter typisk front- og bagplader. This plasma ex-tractor or -ekspressor typically comprise front and back plates. De to plader er hængslet sammen ved deres nedre ender 15 og sidder fjederforspændt mod hinanden således, at der udvikles et tryk på ca. The two plates are hinged together at their lower ends 15 and sits spring biased against each other so as to develop a pressure of about 90 mm Hg i det indre af posen. 90 mm Hg in the interior of the bag.

Med blodopsamlingsposen anbragt mellem de to plader åbnes en ventil, en forsegling eller et lukke i eller på det fleksible rør, hvilket tillader, at de ovenstående PRP 20 strømmer ind i en første satellitpose. With the blood collection bag positioned between the two plates, a valve, a seal or a closure in or on the flexible tube, which allows the above PRP 20 flows into a first satellite bag. Efterhånden som PRP strømmer ud af blodopsamlingsposen, stiger grænsefladen med PRC. As the PRP flows out of the blood collection bag, increases the interface with the PRC. I gængs praksis må operatøren omhyggeligt iagttage positionen af grænsefladen, efterhånden som denne stiger, og afspærre forbindelsesrøret, når der efter hans bedømmelse 25 er overført så meget PRP som muligt, uden at man tillader røde blodlegemer at træde ind i den første satellitpose. In current practice the operator must carefully observe the position of the interface, as this increases, and will cut off the connecting tube when, in his review 25 is transferred as much PRP as possible, without allowing red cells to enter the first satellite bag.

Dette er en arbejdsintensiv og tidsrøvende operation, under hvilken operatøren visuelt må overvåge posen og velovervejet og arbitrært afgøre, når der skal lukkes af for det forbin-* 30 dende rør. This is a labor-intensive and time-consuming operation during which the operator must visually monitor the bag and judiciously and arbitrarily determine when to be closed by the connection of the connecting tube 30 *.

Blodopsamlingsposen, der nu kun indeholder PRC, kan frigøres og opbevares ved 4°C, indtil den skal anvendes til transfusion til en patient, eller en ventil eller forsegling i røret kan åbnes således, at PRC kan overføres til en sa-35 tellitpose, idet der enten anvendes det tryk, der frembringes af plasma-ekstraktoren, eller ved anbringelse af blodopsam- The blood collection bag, now containing only PRC, may be detached and stored at 4 ° C until required for transfusion to a patient, or a valve or seal in the tubing may be opened so that the PRC may be transferred to the SA-35 tellitpose in that using either the pressure generated by the plasma extractor, or by placing the blodopsam-

DK 175916 B1 I In DK 175916 B1

lingsapparatet i en trykmanchet, eller ved elevering til H grinding apparatus in a pressure cuff, or by elevation to H

opnåelse af strømning ved tyngdekraftens hjælp. achieve flow by gravity. H H

(4) Den PRP-indeholdende satellitpose sammen med en H (4) The PRP-containing satellite bag, together with an H

anden satellitpose fjernes derpå fra ekstraktoren og centri- H another satellite bag, is then removed from the extractor and centrifugal H

5 fugeres ved en forøget G-kraft (centrifugering ved høj ha- ' I 5 fugeres at an elevated G force (at high centrifugation HA 'I

stighed eller "hard-spin”-centrifugering) med tiden og ha- H speed or "hard-spin" centrifugation) with the time and HA H

stigheden indstillet således, at blodpladerne koncentreres ” I rate of set such that the platelets are concentrated "in

i den nedre del af PRP-posen. in the lower portion of the PRP bag. Når centrifugeringen er fuld- H When the centrifugation is full-H

stændig, indeholder PRP-posen sedimenterede blodplader i I -employed, PRP bag contains sedimented platelets in the I

10 sin nedre del og klart plasma i sin øvre del. 10 its lower portion and clear plasma in its upper portion. H H

(5) PRP-posen anbringes derpå i plasma-ekstraktoren, H (5) The PRP bag is then placed in the plasma extractor, H

og det meste af det klare plasma trykkes ud i en satellit- H and most of the clear plasma is expressed into a satellite H

pose, hvorved man efterlader PRP-posen indeholdende kun de H bag, thereby leaving the PRP bag containing only the H

sedimenterede blodplader og ca. sedimented platelets and about 50 ml plasma. 50 ml of plasma. I et efterføl- H In a subsequent H

15 gende trin dispergeres dette blodplade-præparat derpå til H 15 the steps of dispersing this platelet composition is then to H

dannelse af blodplade-koncentrat (PC). formation of platelet concentrate (PC). PRP-posen, der nu PRP bag, now

indeholder et PC-produkt, frigøres derefter og opbevares i I containing a PC product, then released and stored in

op til 5 døgn ved 20-24°C, indtil den kræves til en trans- H up to five days at 20-24 ° C until required for a trans H

fusion af blodplader. concentration of platelets. Multiple enheder af blodplader, f.eks. Multiple units of platelets, for example. I IN

20 fra seks til ti donorer, såfremt der er tale om transfusion I 20 from six to ten donors, in the case of transfusion In

til en voksen patient, kan sammenbringes i en enkelt blod- H for an adult patient may be brought together in a single blood-H

plade-transfusion. platelet transfusion. H H

(6) Plasmaet i satellitposen kan selv anvendes til H (6) The plasma in the satellite bag may itself be used to H

transfusion til en patient, eller det kan adskilles ved H transfusion to a patient, or it may be separated by H

25 komplekse processer i en række andre værdifulde produkter. 25 complex processes in a number of other valuable products. H H

Almindeligt anvendte systemer, udover CPDA-1, omfatter H Commonly used systems other than CPDA-1 include H

Adsol, Nutricell og SAG-M. ADSol, Nutricell and SAG-M. I disse sidstnævnte systemer H In these latter systems H

indeholder opsamlingsposen kun anti-koagulerende middel, og H the collection bag contains only anti-coagulant, and H

næringsstofopløsningen kan i forvejen være anbragt i en I nutrient solution may in advance be positioned in an I

30 satellitpose. 30 satellite bag. Denne næringsstofopløsning overføres i PRC- * I This nutrient solution is transferred in PRC * In

produktet, efter at PRP er blevet adskilt fra PRC, hvorved H the product after the PRP has been separated from the PRC, wherein the H

der opnås et højere udbytte af plasma og længere opbevarings- H there is obtained a higher yield of plasma and longer storage H

levetid for PRC-produktet. life for the PRC product. H H

I betragtning heraf er der et voksende behov for et H In view of this, there is a growing need for a H

35 effektivt system og en effektiv metode til adskillelse af H 35 effective system and an efficient method for the separation of H

et biologisk fluidum, f.eks. a biological fluid, for example. helblod, i dets bestanddele. whole blood, into its components. H H

DK 175916 B1 5 DK 175 916 B1 5

Blodbank-personale har reageret på det forøgede behov for blodbestanddele ved forsøg på at forøge PRC- og PC-udbytter på en række forskellige måder. Blood bank personnel have responded to the increased demand for blood components by attempting to increase PRC and PC yields in a number of ways. Ved adskillelse af PRC- og PRP-fraktionerne, f.eks. By separating the PRC and PRP fractions, for example. trin 3 ovenfor, har blodbank-per-5 sonale forsøgt at udpresse mere PRP inden standsning af strømningen fra blodopsamlingsposen, men dette har ofte vist sig ikke at være produktivt, eftersom PRP og PC, som dernæst ekstraheres derfra, hyppigt forurenes af røde blodlegemer, hvilket giver en lyserød eller rød farve for det 10 normalt lysegule PC. step 3 above, blood bank-per-5 sonale attempted to extrude more PRP prior to stopping flow from the blood collection bag, but this has often proved to be counterproductive, since the PRP, and the PC, which is then extracted therefrom, are frequently contaminated by red cells, giving a pink or red color of the 10 normally light yellow PC. Tilstedeværelsen af røde blodlegemer i PC er i så høj.grad uønsket, at lyserødt eller rødt PC ofte kasseres eller underkastes gencentrifugering, idet begge operationer forøger driftsomkostningerne og er arbejdsinten-sive. The presence of red cells in PC is so høj.grad undesirable that pink or red PC is often discarded or subjected to recentrifugation, both of which operations increase the operating costs and are labor-intensive. Som et resultat heraf må blodbank-personale være for 15 forsigtigt ved at standse strømningen af PRP, før det er blevet fuldstændigt presset ud. As a result, blood bank personnel must be gently for 15 by stopping the flow of PRP before it has been fully pressed out. PC er således ikke-forurenet, men det ikke-udpressede plasma, der er værdifuldt, kan gå til spilde. PC is uncontaminated, but the non-pressed plasma that is valuable, may be wasted.

Dette afspejler et andet problem, når det forsøges 20 at forøge udbyttet af individuelle blodbestanddele. This reflects another problem when attempting 20 to increase the yield of individual blood components. Om end hver bestanddel er værdifuld, kan besparelser resulterende fra en forøgelse af udbyttet blive modsvaret af den forøgede arbejdsomkostning, såfremt operatøren for behandlingssystemet kontinuerligt og omhyggeligt skal overvåge systemet for at 25 kunne forøge udbyttet. While each component is valuable, the savings resulting from an increase in the yield will be offset by the increased labor cost, if the operator of the processing system must continuously and carefully monitor the system to 25 to increase the yield.

De her beskrevne apparater og metoder letter de ovenfor beskrevne problemer og tilvejebringer desuden et højere udbytte af PRC og PC med overlegen kvalitet. The herein described apparatus and methods facilitate the above described problems and also provides a higher yield of PRC and PC with superior quality.

Adskillelsen af de forskellige blodbestanddele under 30 anvendelse af centrifugering medfører en række andre problemer. The separation of the various blood fractions during 30 use of centrifugation results in a number of other problems. Når eksempelvis PRP centrifugeres til opnåelse af et lag, der hovedsageligt består af blodplader koncentreret ved bunden af den PRP-holdige pose, f.eks. For example, when PRP is centrifuged to obtain a layer consisting mainly of platelets concentrated at the bottom of the PRP-containing bag, for example. i trin 4 ovenfor, har de således koncentrerede blodplader tendens til at danne 35 et tæt aggregat, der skal dispergeres i plasma til dannelse af blodplade-koncentrat. in step 4 above, the platelets so concentrated tend to form a dense aggregate 35 to be dispersed in plasma to form platelet concentrate. Dispersionstrinet udføres i almin- Dispersionstrinet performed in almin-

DK 175916 B1 I In DK 175916 B1

delighed ved forsigtig blanding, f.eks. mortality by gentle mixing, for example. ved anbringelse af H by placing H

posen på et bevægeligt bord, der roterer med en skråstillet H the bag on a moving table which rotates with an inclined H

bevægelse til behandling. movement to the treatment. Denne blanding kræver adskillige H This mixing requires several H

timer, en potentielt uønsket forsinkelse, og menes af mange H hours, a potentially undesirable delay, and is believed by many H

5 research-sagkyndige at frembringe et partielt aggregeret ' I Research 5-experts to produce a partially aggregated 'I

blodplade-koncentrat. platelet concentrate. Det menes endvidere, at blodpladerne I It is further believed that the platelets

kan blive beskadiget af de kræfter, der påvirker dem under ' I can be damaged by the forces acting on them during 'In

centrifugering. centrifugation. I IN

Endvidere er det et problem i forbindelse med adskil- I Furthermore, it is a problem associated with separation I

10 leisen af forskellige blodbestanddele under anvendelse af I 10 Leisen of various blood components using the I

et multipelt posesystem og centrifugering, at i høj grad I a multiple bag system and centrifugation, to a large extent in

værdifulde blodbestanddele bliver indfanget i de forbindel- I valuable blood components become trapped in the liaison In

sesledninger, der forbinder de forskellelige poser, og i I sesledninger connecting the differences pouches, and I

de forskellige organer, der kan anvendes i systemet. the various means which can be used in the system. I IN

15 Konventionelle behandlings- og opbevaringsmetoder kan også frembyde problemer. 15 Conventional treatment and storage methods can also pose problems. Eksempelvis kan luft, navnlig For example, the air, in particular

oxygen, der er til stede i opbevaret blod og blodbestanddele, I oxygen, present in stored blood and blood components, In

eller i opbevaringsbeholderen, føre til en forringelse af I or in the storage container, may lead to a deterioration of the I

kvaliteten af blodbestanddelene og kan formindske deres I the quality of the blood components and may decrease their I

20 opbevaringslevetid. 20 shelf-life. Mere specifikt kan oxygen associeres I More particularly, oxygen may be associated with the

med en forøget metabolisk hastighed {under glycolyse), der H with an increased metabolic rate {during glycolysis), which H

kan føre til formindsket opbevaringslevetid og formindsket I can lead to reduced shelf life and reduced in

levedygtighed og funktion af hele blodlegemer. viability and function of whole blood cells. Eksempelvis I For example, in

metaboliserer røde blodlegemer under opbevaring glucose, I red blood cells metabolize glucose during storage, In

25 idet der dannes mælkesyre og pyrodruesyre. 25 with the formation of lactic acid and pyruvic acid. Disse syrer ned- I These acids reduce I

sætter mediets pH-værdi, hvilket igen formindsker metaboliske I bring pH of the medium, which in turn decreases metabolic In

funktioner. functions. Endvidere kan tilstedeværelsen af luft eller I Furthermore, the presence of air or in

gas i satellitposen frembyde en risiko, når en patient mod- I gas in the satellite bag present a risk when a patient is received in

tager transfusion med en blodbestanddel. takes transfusion of a blood component. Eksempelvis kan så I For example, that ye

30 lidt som 5 ml luft eller gas forårsage alvorlig beskadigelse . 30 little as 5 ml of air or gas cause serious damage. I IN

eller død. or death. Til trods for den ødelæggende virkning af oxygen H Despite the deleterious effect of oxygen H

på opbevaringslevetiden og kvaliteten af blod og blodbe- H on shelf life and quality of blood and blodbe- H

standdele har den kendte teknik ikke bidraget til at afhjælpe H constituents, the prior art does not helped to overcome H

behovet for at fjerne gasser fra blodbehandlingssystemer H the need to remove gases from blood processing systems H

35 under opsamling og behandling. 35 during collection and processing. H H

Udover de ovenfor angivne bestanddele indeholder H In addition to the above ingredients containing H

DK 175916 B1 7 helblod hvide blodlegemer (kollektivt kendt som leucocyter) af forskellige typer, af hvilke de vigtigste er granulocyter og lymphocyter. DK B1 175 916 7 white blood cells, whole blood (collectively known as leucocytes) of various types, of which the most important are granulocytes and lymphocytes. Hvide blodlegemer giver beskyttelse mod infektion med bakterier og vira. White blood cells provide protection against infection by bacteria and viruses. Transfusionen af blodbe-5 standdele, der ikke er blevet befriet for leucocyter, er ikke uden risiko for den patient, der modtager transfusionen. The transfusion of blodbe-5 constituents that have not been liberated from leucocytes, is not without risk to the patient receiving the transfusion.

Nogle af disse risici er angivet nærmere i US patentskrift nr. 4.923.620 og i US patentskrift nr. 4.880.548, hvortil der henvises. Some of these risks are detailed in U.S. Pat. No. 4,923,620 and in U.S. Pat. No. 4,880,548, incorporated herein by reference.

10 Ved den ovenfor beskrevne centrifugeringsmetode til adskillelse af blod i de tre grundlæggende fraktioner er leucocyterne til stede i væsentlige mængder i både fraktionerne med de pakkede røde blodlegemer og med det blodplade -rige plasma. 10 In the above described centrifugal method for separating blood into the three basic fractions, the leucocytes are present in substantial amounts in both fractions with the packed red blood cells and the platelet-rich plasma. Det er nu generelt accepteret, at det i høj 15 grad er ønskeligt at formindske leucocyt-koncentrationen i disse blodbestanddele til et så lavt niveau som muligt. It is now generally accepted that it is in the high 15 degree is desirable to reduce the leucocyte concentration of these blood components to as low a level as possible. Om end der ikke findes noget fast kriterium, er det generelt accepteret, at mange af de uønskede virkninger ved transfusion ville blive reduceret, såfremt leucocyt-indholdet 20 blev reduceret med en faktor på ca. Although there is no fixed criterion, it is generally accepted that many of the undesirable effects of transfusion would be reduced if the leukocyte content 20 was reduced by a factor of approximately 100 eller mere forud for indgivelsen til patienten. 100 or more prior to administration to the patient. Dette svarer til omtrentlig en formindskelse af det gennemsnitlige totale indhold af leucocyter i en enkelt enhed af PRC til mindre end ca. This corresponds to approximately a reduction of the average total content of leucocytes in a single unit of PRC to less than about 1 x 106, og i en enhed af PRP eller PC til mindre end ca. 1 x 106, and in a unit of PRP or PC to less than about 1 x 25 105. Organer, der tidligere er blevet udviklet ved forsøg på at opnå dette formål, har været baseret på anvendelsen af pakkede fibre og er generelt blevet refereret til som filtre. 1 x 25 105. Entities that have previously been developed in attempts to achieve this objective have been based on the use of packed fibers and have generally been referred to as filters. Det fremgår imidlertid, at fremgangsmåder under anvendelse af filtrering baseret på separation efter stør-" 30 relse af to grunde ikke kan føre frem. For det første kan leucocyter være større end ca. 15μτη, f.eks. granulocyter og macrocyter, ned til en så ringe størrelse som 5-7 μτη, f.eks. lymphocyter. Tilsammen repræsenterer granulocyter og lymphocyter hovedandelen af alle leucocyterne i normalt blod. It is apparent, however, that methods utilizing filtration based on separation by stør- "30 size for two reasons can not lead forward. First, leucocytes be greater than about 15μτη, for example. Granulocytes and macrocyter, down to a such a small size as 5-7 μτη, eg. lymphocytes. Together, granulocytes and lymphocytes represent the major proportion of all of the leucocytes in normal blood.

35 Røde blodlegemer har en diameter på ca. 35 Red blood cells have a diameter of about 7 μτη, dvs. 7 μτη, i.e. at de har ca. that they have approximately samme størrelse som lymphocyter, der er en af de to the same size as lymphocytes, one of the two

DK 175916 B1 I In DK 175916 B1

hovedklasser af leucocyter, der skal fjernes. major classes of leucocytes which must be removed. For det andet H Secondly H

deformeres alle disse celler således, at de er i stand til H all of these cells deform so that they are able to H

at passere gennem meget mindre åbninger end deres normale I to pass through much smaller openings than their normal I

størrelse. size. Det er således i udstrakt grad blevet accepteret, I Thus, it is widely accepted, I

5 at fjernelse af leucocyter hovedsageligt foretages ved ad- I 5 to remove leucocytes mainly is performed by ad- In

sorption på e indre overflader af porøse medier i stedet I e sorption on inner surfaces of porous media, rather than in

for ved filtrering. for by filtration. I IN

Leucocyt-f jernel se er særlig betydningsfuld med hensyn I Leucocyte f jernel view is particularly significant in terms of In

til en blodbestanddel såsom PC. to a blood component such as PC. Blodplade-koncentrater frem- I Platelet concentrates produced in

10 stillet ved den differentielle centrifugering af blodbe- 10 provided in the differential centrifugation to blood

standdele vil have varierende niveauer af leucocyt-forurening I constituents will have varying levels of leucocyte contamination in

i relation til tiden og størrelsen af den kraft, der udvikles H in relation to the time and magnitude of the force developed H

under centrifugering. during centrifugation. Niveauet for leucocyt-forurening i I The level of leucocyte contamination in the I

ikke -filtrerede, konventionelle blodplade-præparater af I not -filtrerede, conventional platelet preparations of I

15 seks til ti sammenførte enheder ligger generelt ved et niveau I 15:06 to ten pooled units is generally at a level in the

på ca. about 5 x 108 eller højere. 5 x 108 or higher. Det er blevet påvist, at leuco- I It has been shown that the leuco In

cyt-fjernelseseffektiviteter på 81-85% er tilstrækkelige cyt-removal efficiencies of 81-85% are sufficient

til at formindske forekomsten af febrile reaktioner ved I to decrease the incidence of febrile reactions by I

blodplade-transfusioner. platelet transfusions. Adskillige andre, for nylig udførte I Several other, recently conducted in

20 studier viser en reduktion i alloimmunisering og blodplade- I 20 studies show a reduction in alloimmunization and platelet In

modstandsdygtighed ved niveauer for leucocyt-forurening I resistance at levels of leucocyte contamination in

under ca. below about lx 107 pr. per 107 lx. enhed. unit. For en enkelt enhed af PC, der For a single unit of PC that

viser et gennemsnitligt leucocyt-forureningsniveau (under I shows an average leucocyte contamination level (under I

gængs praksis) på ca. current practice) of about 7 x 107 leucocyter, er målet efter H 7 x 107 leucocytes, the goal after H

25 filtrering mindre end 1 x 106 leucocyter. 25 filtration less than 1 x 106 leucocytes. De eksisterende I Existing In

undersøgelser antyder derfor ønskeligheden af i det mindste H Therefore, studies suggest the desirability of at least H

en to logaritmers (99%) reduktion af leucocyt-forurening. one two log (99%) reduction of leucocyte contamination. I IN

Mere nyligt udførte undersøgelser antyder, at en tre loga- H More recent studies suggest that the one three loga- H

ritmers (99,9%) eller endog en fire logaritmers (99,99%) ritmers (99.9%) or even four log (99.99%)

30 reduktion ville være signifikant mere gavnlig. 30 reduction would be significantly more beneficial. „ I "In

Et yderligere ønskeligt kriterium er at begrænse I A further desirable criterion is to restrict In

blodpladetab til ca. platelet loss to about 15% eller mindre af den oprindelige I 15% or less of the original I

blodpladekoncentration. platelet concentration. Blodplader er almindeligt kendte H Platelets are generally known H

for at være "klæbende", et udtryk, der afspejler tendensen H for being "sticky", an expression reflecting the tendency H

35 for blodplader, der er suspenderet i blodplasma, til at I 35 for platelets suspended in blood plasma, to I

hænge ved enhver ikke-fysiologisk overflade, for hvilken de H cling to any non-physiological surface to which the H

DK 175916 B1 9 udsættes. DK 175916 B1 9 are reserved. Under mange omstændigheder hænger de også kraftigt sammen med hverandre. Under many circumstances, they also strongly related with each other.

I ethvert system, der afhænger af filtrering til fjernelse af leucocyter fra en blodpladesuspension, vil der 5 være en væsentlig kontakt mellem blodplader og de indre overflader af filtersammensætningen. In any system which depends upon filtration to remove leucocytes from a platelet suspension, there will be a 5 substantial contact between platelets and the internal surfaces of the filter assembly. Filtersammensætningen må være således beskaffen, at blodpladerne har minimal adhæsion til og ikke signifikant påvirkes på uønsket måde ved kontakt med filtersammensætningens indre overflader. The filter assembly may be designed such that the platelets have minimal adhesion to, and not significantly affected in an undesirable manner when in contact with inner surfaces filtersammensætningens.

10 Hvis leucocyt-fjernelsesorganet indeholder en porøs struktur, har mikroaggregater, geler, fibrin, fibrinogen og fedt-småkugler tendens til at samle sig på eller i porerne og forårsage blokering, der inhiberer strømningen. 10 If the leucocyte removal means includes a porous structure, microaggregates, gels, fibrin, fibrinogen and fat globules tend to collect on or within the pores, causing blockage which inhibits flow. Konventionelle processer, ved hvilke filteret til fjernelse af 15 leucocyter fra PRC, for-konditioneres ved at føre saltvandsopløsning gennem filtersammensætningen med eller uden en saltvandsskylning efter filtreringen, er uønskede, eftersom væskeindholdet i transfusionen forøges i uønsket høj grad, hvorved patientens cirkulatoriske system overbelastes poten-20 tielt med væske. Conventional processes in which the filter for removing 15 leucocytes from PRC, pre-conditioned by passing saline through the filter assembly with or without a saline flush following the filtration, are undesirable because the liquid content of the transfusion is increased undesirably high level, whereby the patient's circulatory system is overloaded paw -20 tielt with liquid. Et formål med en udførelsesform for den foreliggende opfindelse er tilvejebringelse af et leucocyt-fjernelsesorgan, der fjerner leucocyter og disse andre elementer med høj effektivitet og uden tilstopning, ikke kræver nogen for-konditionering forud for behandling af PRC, der 25 stammer fra frisk aftappet blod, og ikke kræver skylning efter filtrering til genvinding af røde blodlegemer, der forbliver i filteret. An object of an embodiment of the present invention is to provide a leukocyte removal means which removes leucocytes and these other elements with high efficiency and without clogging, requires no preconditioning prior to processing PRC to 25 derived from freshly drawn blood , and does not require rinsing after filtration in the recovery of red blood cells that remain in the filter.

På grund af de høje omkostninger og den begrænsede tilgængelighed af blodbestanddele bør et organ, der omfatter 30 et porøst medium, som anvendes til at fjerne leucocyter fra biologisk fluidum, levere den størst mulige andel af bestanddelen, der er til stede i donor-blodet. Because of the high cost and limited availability of blood components should be a body which comprises 30 is a porous medium which is used to remove leucocytes from biological fluid, deliver the highest possible proportion of the component that is present in the donor blood. Et ideelt organ til leucocyt-fjernelse fra PRC eller PRP vil være forbundet med ringe omkostninger, være forholdsvis lille og være i stand 35 til hurtigt at behandle blodbestanddele opnået fra ca. An ideal device for leucocyte depletion of PRC or PRP would be associated with a low cost, be relatively small and be in a position 35 to expedite the examination of blood components obtained from about én enhed eller mere af biologisk fluidum, f.eks. one unit or more of biological fluid, for example. donor-helblod, donated whole blood,

DK 175916 B1 I In DK 175916 B1

i løbet af f.eks. in the course of example. mindre end 1 time. less than 1 hour. Ideelt set skal dette I Ideally, this I

organ reducere leucocytindholdet til det lavest mulige ni- I body reduce the leucocyte content to the lowest nine-In

veau, idet udbyttet af en værdifuld blodbestanddel maksim- I level, the yield of a valuable blood component maksim- In

eres, medens en dyr, sofistikeret, arbejdsintensiv indsats I tion, while an expensive, sophisticated, labor intensive effort in

5 af operatøren af systemet minimeres. 5 by the operator of the system is minimized. Udbyttet af blodbe- I Proceeds to blood In

standdelen bør maksimeres, medens der samtidig leveres en I able portion should be maximized, while at the same time be provided with an I

levedygtig og fysiologisk aktiv bestanddel, f.eks. viable and physiologically active ingredient, for example. ved mi- I In the micro-

nimering af beskadigelse på grund af centrifugering og/eller minimization of damage due to centrifugation, and / or

tilstedeværelsen af luft eller gas. the presence of air or gas. Det kan også være fore- I It may also be PREVIOUS In

10 trukkent, at det PRC-porøse medium er i stand til at fjerne I 10 trukkent that the PRC porous medium is capable of removing at

blodplader såvel som fibrinogen, .fibrinstrenge, meget små H platelet as well as fibrinogen, .fibrinstrenge, very small H

fedt-småkugler og andre bestanddele såsom mikroaggregater, H fat globules, and other components such as microaggregates, H

der kan være til stede i helblod. which may be present in whole blood. H H

De følgende definitioner anvendes i forbindelse med H The following definitions are used in connection with the H

15 beskrivelsen af den foreliggende opfindelse: H 15 the description of the present invention: H

(A) Blodprodukt eller biologisk fluidum: antikoagule- H (A) Blood Product or Biological Fluid: anticoagulated H

ret helblod (AWB); right whole blood (AWB); pakkede røde blodlegemer opnået fra AWB; packed red cells obtained from AWB; I IN

blodplade-rigt plasma (PRP) opnået fra AWB; platelet-rich plasma (PRP) obtained from AWB; blodplade-kon- I platelet-con- In

centrat (PC) opnået fra AWB eller PRP; concentrate (PC) obtained from AWB or PRP; plasma opnået fra H plasma obtained from the H

20 AWB eller PRP; 20 AWB or PRP; røde blodlegemer adskilt fra plasma og gen- H red cells separated from plasma and re-H

suspenderet i fysiologisk fluidum; suspended in physiological fluid; og blodplader adskilt fra I and platelets separated from the I

plasma og gensuspenderet i fysiologisk fluidum. plasma and resuspended in physiological fluid. Blodprodukt I Blood product in

eller biologisk fluidum omfatter også ethvert behandlet eller I or biological fluid also includes any treated or I

ubehandlet fluidum, der er associeret med levende organismer, I untreated fluid associated with living organisms, In

25 især blod, herunder helblod, varmt eller koldt blod, og I 25 particularly blood, including whole blood, warm or cold blood, and I

opbevaret eller frisk blod; stored or fresh blood; behandlet blod, f.eks. treated blood, for example. blod I In blood

fortyndet med en fysiologisk opløsning, omfattende, men I diluted with a physiological solution, including but I

ikke begrænset til saltvandsopløsninger, næringsmiddelopløs- I not limited to saline, næringsmiddelopløs- In

ninger og/eller anti-koaguleringsmiddelopløsninger; solutions and / or anti-koaguleringsmiddelopløsninger; én eller I In one or

30 flere blodbestanddele, f.eks. 30 more blood components, for example. blodplade-koncentrat (PC), I platelet concentrate (PC), I

blodplade-rigt plasma (PRP), blodplade-frit plasma, blodpla- I platelet-rich plasma (PRP), platelet-free plasma, platelet I

de-fattigt plasma, plasma, eller pakkede røde blodlegemer I de-poor plasma, plasma, or packed red blood cells in the

(PRC); (PRC); analoge blodprodukter afledt af blod eller en blod- bestanddel eller afledt af benmarv. analogous blood products derived from blood or a blood component or derived from bone marrow. Det biologiske fluidum The biological fluid

35 kan indeholde leucocyter eller kan behandles til fjernelse I 35 may include leucocytes, or may be treated to remove I

af leucocyter. leucocytes. Som her anvendt refererer udtrykkene "blod- I As used herein the terms "Blood In

DK 175916 B1 11 produkt" eller "biologisk fluidum" til de ovenfor beskrevne bestanddele og til lignende blodprodukter eller biologiske væsker opnået ved andre midler og med tilsvarende egenskaber. DK 175916 B1 11 product "or" biological fluid "refers to the ingredients described above and to similar blood products or biological fluids obtained by other means and with similar properties.

I overensstemmelse med opfindelsen behandles hvert af disse 5 blodprodukter eller biologiske fluida på den måde, der er beskrevet i nærværende beskrivelse. In accordance with the invention, consider each of the 5 these blood products or biological fluids in the manner described herein.

(B) Enhed af helblod: I blodbanker i USA aftappes der almindeligvis ca. (B) The unit of whole blood: In blood banks in the United States is drained is generally about 450 milliliter (ml) blod fra donoren i en pose, der indeholder et antikoagulationsmiddel til 10 hindring af, at blodet sammenklumper. 450 milliliters (ml) of blood from the donor into a bag which contains an anticoagulant to 10 prevent the blood clumps together. Den aftappede mængde varierer imidlertid fra patient til patient og fra aftapning til aftapning.' The tapped amount, however, varies from patient to patient and from drain to drain. ' I den foreliggende beskrivelse er den mængde, der aftappes under en sådan donorafgivelse, defineret som en enhed af helblod. In the present specification, the quantity drawn during such a donor delivery, defined as a unit of whole blood.

15 (C) Enhed af pakkede røde blodlegemer (PRC), blodpla- de-rigt plasma (PRP) eller blodplade-koncentrat (PC): Som her anvendt er en "enhed" defineret ifølge USA-praksis, og en enhed af PRC, PRP, PC eller af røde blodlegemer eller blodplader i fysiologisk fluidum eller plasma er den mængde, 20 der er afledt af én enhed af helblod. 15 (C) The unit of packed red cells (PRC), platelet-rich plasma (PRP) or platelet concentrate (PC): As used herein, a "unit" is defined according to US practice, and a unit of PRC, PRP, PC, or of red cells or platelets in physiological fluid or plasma, is the quantity 20 that is derived from one unit of whole blood. Betegnelsen kan også referere til den mængde, der aftappes under en enkelt donorafgivelse. The term can also refer to the quantity drawn during a single donor set. Typisk varierer rumfanget af en enhed. Typically the volume of a device. Eksempelvis varierer rumfanget af en enhed af PRC betydeligt, afhængigt af hæmatocriten (procentmængden af røde blodlegemer efter 25 rumfang) for det aftappede helblod, der almindeligvis ligger i området fra ca. For example, varying the volume of a unit of PRC considerably, depending on hæmatocriten (percentage of red blood cells by 25 volumes) of the bottled whole blood, generally being in the range from about 37 til ca. To about 37 54%. 54%. Den ledsagende hæmatocrit af PRC, der varierer i området fra ca. The concomitant hematocrit of PRC, which varies in the range of about 50 til over 80%, afhænger delvis af, om udbyttet af ét eller et andet blodprodukt skal minimeres.. De fleste PRC-enheder ligger i om-30 rådet fra ca. 50 to 80%, depends in part on whether the yield of one or another blood product must be minimized .. Most PRC units are in the 30 council from about 170 til ca. 170 to ca. 300 ml, men variation under og over disse størrelser er ikke usædvanlig. 300 ml, but variation below and above these values ​​are not uncommon. Multiple enheder af nogle blodbestanddele, navnlig blodplader, kan slås sammen eller kombineres, typisk ved kombination af seks eller flere enheder. Multiple units of some blood components, particularly platelets, may be pooled or combined, typically by combining six or more units.

35 (D) Plasmafattigt fluidum: Et plasmafattigt fluidum refererer til ethvert biologisk fluidum, fra hvilket der er 35 (D) Plasma-poor Fluid: A plasma-poor fluid refers to any biological fluid from which the

DK 175916 B1 I In DK 175916 B1

blevet fjernet en eller anden mængde plasma, f.eks. been removed for some amount of plasma, for example. det I the ten

blodpladerige fluidum, der fås, når plasma adskilles fra PRP, I platelet-rich fluid obtained when plasma is separated from PRP, In

eller det fluidum, der bliver tilbage, efter at plasma er H or the fluid which remains after plasma is H

fjernet fra helblod. removed from the whole blood. I IN

5 (E) Porøst medium: referer til det porøse medium, I 5 (E) Porous medium: refers to the porous medium, I

gennem hvilket én eller flere blodbestanddele eller biolo- giske fluida passerer. through which one or more blood components or biological fluids pass. Det PRC-porøse medium fjerner leuco- The PRC porous medium removes leuco

cyter fra den bestanddel, der består af pakkede røde blod- I cyter from the component consisting of packed red blood In

legemer. bodies. Blodplade- eller det PRP-porøse medium refererer H The platelet or PRP porous medium refers H

10 generisk til ethvert af de medier, der fjerner leucocyter I 10 generic to any media that removes leucocytes In

fra ikke-PRC-blodbestanddelene, dvs. from the non-PRC blood components, i.e., fra PRP eller PC. from PRP or PC. Bar- Bar-

rieremediet for røde blodlegemer blokerer passagen af røde I arteries medium for red blood cells block the passage of red I

blodlegemer og fjerner leucocyter fra PRP i en større eller I blood cells and depletes leucocytes from PRP to a greater or In

mindre grad, idet passage af blodplader tillades. to a lesser extent, the passage of platelets is allowed. I IN

15 Som angivet nærmere i det følgende kan det porøse I 15 As set forth in more detail below, the porous I

medium, der skal anvendes sammen med PRC, dannes ud fra I medium to be used with PRC, is formed from the I

ethvert naturligt eller syntetisk fibermateriale (eller ud I any natural or synthetic fiber material (or in I

fra andre materialer med lignende overfladeareal og porestør- I from other materials of similar surface area and pore In

relse), der er foreneligt med blod. size) compatible with blood. Det porøse medium kan I The porous medium can

20 forblive ubehandlet. 20 remain untreated. Fortrinsvis ligger den kritiske fugtede I Preferably, the critical wetting In

overfladespænding (CWST) for det porøse medium inden for et surface tension (CWST) of the porous medium within a

betemt område som angivet nedenfor og som dikteret af dets I betemt area as indicated below and as dictated by its I

tilsigtede anvendelse. intended use. Poreoverfladerne i mediet kan modi- I The pore surfaces of the medium can be modi- In

ficeres eller behandles til opnåelse af den ønskede CWST. ficeres or treated to achieve the desired CWST. I IN

25 Eksempelvis er CWST for et PRC-porøst medium typisk over I 25 For example, the CWST of a PRC porous medium is typically above I

ca. ca. 53 dyn/cm. 53 dynes / cm. I IN

Det porøse medium til anvendelse sammen med PRP kan I The porous medium for use with PRP may be I

fremstilles ud fra ethvert naturligt eller syntetisk fiber- . be prepared from any natural or synthetic fiber. I IN

materiale eller andet porøst materiale, der er foreneligt I material or any other porous material that is compatible I

30 med blod. 30 with blood. Det porøse medium kan forblive ubehandlet. The porous medium may remain untreated. For- . For- . I IN

trinsvis ligger CWST-værdien og zeta-potentialet for det I preferably located CWST and zeta potential of the In

porøse medium inden for visse grænser som angivet nedenfor I porous medium within certain limits, as indicated below,

og som dikteret af dets tilsigtede anvendelse. and as dictated by its intended use. Eksempelvis I For example, in

ligger CWST for et PRP-porøst medium typisk over ca. is the CWST of a PRP porous medium is typically above about 70 I In 70

35 dyn/cm. 35 dynes / cm. I IN

De her omhandlede porøse medier kan være forbundet I The instant porous media can be connected in

DK 175916 B1 13 til en ledning, der er anbragt mellem beholderne og kan være anbragt i et hus, der igen kan være forbundet til ledningen. DK 175 916 B1 to a conduit 13 which is disposed between the containers and may be arranged in a housing, which in turn may be connected to the conduit. Som anvendt her refererer en filtersammensætning til det porøse medium anbragt i et passende hus. As used herein, a filtering composition for the porous medium positioned in a suitable housing. Et eksempel 5 på en filtersammensætning kan omfatte en leucocyt-f jemelses-sammensætning eller et tilsvarende organ eller en barrieresammensætning eller et barriereorgan for røde blodlegemer. An example 5 of a filter assembly may include a leucocyte f jemelses composition or a similar body or a barrier composition or a barrier means for red blood cells.

Et biologisk fluidumbehandlingssystem, f.eks. A biological fluid treatment system, for example. et blodopsamlings- og behandlingssystem, kan omfatte porøse medier, 10 fortrinsvis som filtersammensætninger. a blood collection and processing system, may comprise porous media, preferably as filter 10 compositions. Fortrinsvis danner det porøse medium en prespasning ved dets kanter, når det er samlet i huset. Preferably the porous medium forms an interference fit at its edges when assembled in the housing.

Det porøse medium kan have konfiguration som et plant ark, et korrugeret ark, et væv eller en membran. The porous medium may have the configuration as a flat sheet, a corrugated sheet, a web or a membrane. Det porøse 15 medium kan være for-formet og konfigureret som hule fibre, om end det ikke er hensigten, at opfindelsen skal begrænses i denne henseende. 15 The porous medium may be pre-formed, and configured as hollow fibers, although it is not intended that the invention be limited in this regard.

(F) Separationsmedium: Et separationsmedium refererer til et porøst medium, der er effektivt til adskillelse af 20 én bestanddel af et biologisk fluidum fra en anden bestanddel. (F) Separation Medium: A separation medium refers to a porous medium effective for separating one component 20 of a biological fluid from another component. Separationsmedierne ifølge opfindelsen er egnede til at lede i det mindste én bestanddel af blodproduktet eller det biologiske fluidum, især plasma, igennem disse, men ikke andre bestanddele af blodproduktet eller det biologiske 25 fluidum, navnlig blodplader og/eller røde blodlegemer. The separation media according to the invention are suitable for passing at least one component of the blood product or biological fluid, particularly plasma, therethrough, but not other components of the blood product or biological 25 fluid, particularly platelets and / or red blood cells.

Som angivet nærmere i det følgende kan separations-mediet til anvendelse i forbindelse med et biologisk fluidum dannes ud fra ethvert naturligt eller syntetisk fibermateriale eller ud fra en porøs eller permeabel membran (eller 30 ud fra andre materialer med lignende overfladeareal og porestørrelse) , der er forenelig med et biologisk fluidum. As set forth in more detail below can be separation medium for use in conjunction with a biological fluid formed from any natural or synthetic fiber or from a porous or permeable membrane (or 30 from other materials of similar surface area and pore size) which had been compatible with a biological fluid. Overfladen af fibrene eller membranen kan være umodificeret eller kan modificeres til opnåelse af en ønsket egenskab. The surface of the fibers or membrane may be unmodified or may be modified to obtain a desired property.

Om end separationsmediet kan forblive ubehandlet, behandles 35 fibrene eller membranen fortrinsvis for at gøre dem endnu mere effektive til adskillelse af en bestanddel af et bio- Although the separation medium may remain untreated, the fibers 35 are treated or membrane is preferably in order to make them even more effective for separating one component of a bio-

DK 175916 B1 I In DK 175916 B1

logisk fluidum, f.eks. logical fluid, for example. plasma, fra andre bestanddele af en I plasma, from other components of an I

biologisk fluidum, f.eks. biological fluid, for example. blodplader eller røde blodlegemer. platelets or red blood cells. I IN

Separationsmediet behandles fortrinsvis til reducering eller I The separation medium is preferably treated to reduce or I

eliminering af blodplade-vedhængning til mediet. elimination of platelet adhesion to the medium. Enhver I any In

5 behandling, der reducerer eller eliminerer blodplade-ved- 5 treatment which reduces or eliminates platelet ved-

hængning, er omfattet af opfindelsens omfang. hanging, covered by the scope of the invention. Endvidere kan I In addition,

mediet være overflademodificeret som beskrevet i US patent- I the medium may be surface modified as described in U.S. Patent In

skrift nr. 4.880.548, hvortil der henvises, til forøgelse I Nos. 4,880,548, incorporated herein by reference, to the increase in

af den kritiske fugtede overfladespænding (CWST) af mediet I of the critical wetting surface tension (CWST) of the medium in

10 og til at være mindre vedhængende for blodplader. 10 and to be less adherent of platelets. Defineret I defined In

med hensyn til CWST ligger et foretrukkent område for CWST I with respect to CWST is a preferred range for the CWST In

for et her omhandlet separationsmedium over ca. for a present separation medium of ca. 70 dyn/cm, H 70 dyne / cm, H

fortrinsvis over ca. preferably above about 90 dyn/cm. 90 dynes / cm. Mediet kan også underkastes I The medium may also be subjected to in

en gas-plasmabehandling til formindskelse af blodplade-ad- I a gas-plasma treatment for reducing the platelet In ad-

15 hæsion. 15 adhesion. Fortrinsvis ligger den kritiske fugtede overflade- H Preferably, the critical wetting surface H

spænding (CWST) af separationsmediet i et bestemt område I tension (CWST) of the separation medium in a specific area of

som angivet nedenfor og som dikteret af dets tilsigtede I as indicated below and as dictated by its intended I

anvendelse. application. Poreoverfladerne af mediet kan modificeres eller The pore surfaces of the medium may be modified or

behandles til opnåelse af den ønskede CWST-værdi. treated to achieve the desired CWST. H H

20 Separationsmediet kan være for-formet, være et fler- H The separation medium 20 may be pre-formed, may have a multi-H

lags-medium og/eller kan behandles til modificering af over- H layered medium and / or may be treated for modification of over- H

fladen af mediet. surface of the medium. Såfremt der anvendes et fibrøst medium, H Where use is a fibrous medium, H

kan fibrene behandles enten før eller efter formingen af H the fibers may be treated either before or after the formation of H

det fibrøse materiale. the fibrous material. Det foretrækkes at modificere fiber- H It is preferred to modify the fiber H

25 overfladerne før dannelsen af det fibrøse materiale, eftersom H 25 the surfaces prior to formation of the fibrous material, since H

et mere sammenhængende og stærkere produkt fås efter varm H a more coherent and stronger product is obtained after hot H

sammenpresning til dannelse af et integralt filterelement. compression to form an integral filter element. H H

Separationsmediet er fortrinsvis for-formet. The separation medium is preferably pre-formed. H H

Separationsmediet kan være konfigureret på enhver I The separation medium may be configured in any I

30 passende måde, f.eks. 30 suitable manner, for example. som et plant ark, et korrugeret ark, H as a flat sheet, a corrugated sheet, H

et væv, hule fibre eller en membran. a web, hollow fibers or a membrane. H H

(G) Hulrumsrumfanget er det totale rumfang af alle H (G) Voids volume is the total volume of all H

porerne i et porøst medium. the pores in a porous medium. Hulrumsrumfanget udtrykkes i det H The void volume is expressed in the H

følgende som en procentdel af det tilsyneladende rumfang af H the following as a percentage of the apparent volume of H

35 det porøse medium. 35 the porous medium. H H

(H) Måling af fiberoverfladeareal og af gennemsnitlig H (H) Measurement of fiber surface area and the average H

DK 175916 B1 15 i fiberdiameter: I forbindelse med opfindelsen betegnes en nyttig teknik til måling af fiberoverfladeareal, f.eks. DK 175916 B1 15 of the fiber diameter: For the purpose of the invention is termed a useful technique for the measurement of fiber surface area, for example. ved gas-adsorption, generelt som "BET"-målingen. by gas adsorption, is generally as "BET" measurement on. Overfladearealet af smelteblæste væv kan anvendes til beregning af 5 den gennemsnitlige fiberdiameter, idet der anvendes PBT som et eksempel: The surface area of ​​melt blown webs can be used to calculate the 5 the average fiber diameter, using PBT as an example:

Totalt rumfang af fiber i 1 gram = —cm3 Total volume of fiber in 1 gram = -cm3

1,3 B 1.3 B

10 (hvor 1,38 = fibermassefylde af PBT ig/cm3) hvorfor —— —— = --- (1) 4 1,38 15 10 (where 1.38 = fiber density of PBT, g / cm 3) therefore - - = --- (1) 4 1.38 15

Arealet af fiberen er mdL « Af (2) The area of ​​the fiber is MDL "of (2)

Division af (1) med (2) giver —= -1- Division of (1) to (2) gives - = 1-

4 1,38A 4 1,38A

20 og d = -^- = 2,9 eller (0,345Af)-1 1.38A Af r ^vor L = den totale længde i cm af 1 g fiber, d = gennemsnitlig fiberdiameter i cm, og 25 Af = fiberoverfladeareal i cm2/g. 20 and d = - ^ - = 2.9 or (0,345Af) -1 1.38A of r ^ vor L = the total length in cm of 1 gram of fiber, d = average fiber diameter in centimeters, and 25 = fiber surface area in cm 2 / g.

Hvis enhederne for d er mikrometer, bliver enhederne for Af m2/g, hvilket vil blive anvendt i det følgende. If the units of d are micrometers, the units of of the M2 / g, which will be used hereinafter.

(I) Kritisk fugtet overfladesplnding: Som angivet i 30 US patentskrift nr. 4.880.548 kan CWST-værdien for et porøst medium bestemmes med individuel påføring på dets overflade af en række væsker med overfladespændinger, der varierer med 2-4 dyn/cm, hvorpå man iagttager adsorptionen eller ikke-adsorptionen af hver væske i tidens løb. (I) Critical moistened overfladesplnding: As stated in 30 U.S. Pat. No. 4,880,548 can CWST of a porous medium is determined by individually applying to its surface a series of liquids with surface tensions varying by 2 to 4 dynes / cm, which one observer adsorption or non-adsorption of each liquid over time. CWST-værdien 35 for et porøst medium i enheden dyn/cm defineres som middelværdien af overfladespændingen af den væske, der absorberes, og middelværdien af overfladespændingen af væsken med tilstødende overfladespænding, der ikke absorberes inden 35 CWST of a porous medium in units of dyn / cm is defined as the mean value of the surface tension of the liquid to be absorbed, and the mean value of the surface tension of the liquid with the neighboring surface tension which is not absorbed within

DK 175916 B1 I In DK 175916 B1

for en forudbestemt tidsramme. for a predetermined time frame. De absorberede og ikke-absor- B The absorbed and non-absorbed B

berede værdier afhænger principielt af de foreliggende over- B preparing values ​​depend principally on the available over- B

fladekarakteristika for det materiale, ud fra hvilket det B surface characteristics of the material from which the B

porøse medium er fremstillet, og sekundært af det porøse B porous medium is made and secondarily of the porous B

5 mediums porestørrelsekarakteristika. 5 porestørrelsekarakteristika medium. B B

Væsker med overfladespændinger lavere end CWST-værdien B Liquids with surface tensions lower than the CWST B

for et porøst medium vil spontant fugte mediet ved kontakt, B of a porous medium will spontaneously wet the medium on contact, B

og såfremt porerne i mediet forbindes indbyrdes, vil væske B and if the pores of the medium are interconnected, liquid will B

let strømme gennem mediet. easily flow through the medium. Væsker med overfladespændinger I Liquids with surface tensions in

10 højere end CWST-værdien for det porøse medium kan overhovedet B 10 higher than the CWST of the porous medium can at all B

ikke strømme ved lave differentielle tryk eller kan strømme fl not flow at low differential pressures, or may flow fl

ujævnt ved tilstrækkeligt høje differentielle tryk til at B unevenly at sufficiently high differential pressures to B

tvinge væsken gennem det porøse medium. forcing the liquid through the porous medium. Til opnåelse af en B To obtain a B

passende priming af et fibrøst medium med en væske såsom B adequate priming of a fibrous medium with a liquid such as B

15 blod har det fibrøse medium fortrinsvis en CWST-værdi i B 15 has blood, the fibrous medium preferably has a CWST in the B

området fra ca. the range of about 53 dyn/cm eller højere. 53 dynes / cm or higher. B B

For det porøse medium, der anvendes til behandling B For the porous medium which is used to treat B

af PRC, foretrækkes det, at CWST-værdien holdes inden for B of PRC, it is preferred that the CWST be held within the B

et område noget over CWST-værdien for ubehandlet polyester- B a range somewhat above the CWST of untreated polyester B

20 fiber (52 dyn/cm), f.eks. 20 fiber (52 dynes / cm), for example. over ca. over about 53 dyn/cm, og navnlig B 53 dyne / cm, and, in particular B

foretrukket over ca. preferably greater than about 60 dyn/cm. 60 dynes / cm. For det porøse medium, der B For the porous medium which B

anvendes til behandling af PRP foretrækkes det, at CWST- I is used to treat the PRP, it is preferred that CWST- In

værdien holdes i et område over ca. is maintained in a range above about 70 dyn/cm. 70 dynes / cm. B B

(J) Generel procedure til måling af zeta-potentiale: B (J) General procedure for measuring zeta potential: B

25 Zeta-potentiale måles under anvendelse af en prøve udskåret B 25 The zeta potential is measured using a sample cut B

fra en ca. from about 12,7 mm tyk stak af væv. 12.7 mm thick stack of tissues. B B

Zeta-potentialet måles ved anbringelse af prøven i I The zeta potential is measured by placing the sample in the I

en acrylisk filterholder, der holder prøven tæt mellem to B an acrylic filter holder which holds the sample tightly between two B

platintrådssigter 100 x 100 mesh, dvs. platinum wire screens 100 x 100 mesh, i.e., 100 tråde i hver B 100 wires in each B

30 retning pr. 30 per direction. ca. ca. 25,4 mm. 25.4 mm. Maskerne forbindes under anvendelse B The masks are connected using B

af kobbertråd til terminalerne af et Triplett Corporation B of copper wire to the terminals of a Triplett Corporation B

model 3360 volt-ohm-meter, idet masken på opstrømssiden af B model 3360 volt-ohm meter, with the mask on the upstream side of B

prøven forbindes til den positive terminal af måleinstrumen- B the sample is connected to the positive terminal of the gauges B

tet. ment. En pH-pufret opløsning ledes gennem prøven under anven- B A pH-buffered solution was passed through the sample during the application B

35 delse af en trykdifference på ca. 35 APPROVAL of a pressure difference of approximately 1143 mm vandsøjle over B 1143 mm water column of B

filterholderen, og den udstrømmende væske opsamles. the filter holder and the effluent collected. Til B to B

DK 175916 B1 17 målinger ved pH 7 fremstilles der en pufret opløsning ved at sætte 6 ml puffer med en pH-værdi på 7 (Fisher Scientific Co., katalog nr. SB108-500) og 5 ml puffer med pH = 7,4 (Fisher Scientific Co., katalog nr. SB110-500) til 1 liter 5 pyrogenfrit, afioniseret vand. DK 175916 B1 17 measurements at pH 7, a buffered solution by adding 6 ml of buffer having a pH of 7 (Fisher Scientific Co., Cat. No. SB108-500) and 5 ml of buffer with pH = 7.4 ( Fisher Scientific Co., Cat. No. SB110-500) to 1 liter pyrogen-free 5, deionized water. Til målinger ved en pH-værdi på 9 fremstilles der en pufret opløsning ved at sætte 6 ml puffer med en pH-værdi på 9 (Fisher Scientific Co., katalog nr. SB114-500) og 2 ml puffer med en pH-værdi på 10 (Fisher Scientific Co., katalog nr. SB116-500) til en 1 liter pyro-10 genfrit, afioniseret vand. For measurements at pH 9, a buffered solution by adding 6 ml of buffer having a pH of 9 (Fisher Scientific Co., Cat. No. SB114-500) and 2 ml of buffer having a pH of 10 (Fisher Scientific Co., Cat. No. SB116-500) to 1 liter pyrogen-10 genfrit, deionized water. Det elektriske potentiale over filterholderen måles under strømningen (der kræves ca. 30 sekunders strømning for at potentialet kan stabiliseres) og korrigeres for cellepolarisering ved subtraktion derfra af det elektriske potentiale, der måles, når strømningen stand-15 ses. The electrical potential across the filter holder is measured during the flow (required about 30 seconds of flow for the potential to stabilize) and corrected for cell polarization by subtracting from it the electrical potential measured when flow-condition 15 is seen. Under tidsrummet for strømning måles pH-værdien af væsken under anvendelse af et Cole-Parmer model J-5994-10-pH-meter, der er udstyret med en in-line-model J-5993-90-pH-sonde. During the period of flow is measured the pH of the liquid using a Cole-Parmer model J-5994-10 pH meter fitted with an in-line model J-5993-90 pH probe. Ledningsevnen for væsken måles under anvendelse af en Cole-Parmer model J-1481-60-ledningsevnemåler udstyret 20 med en model J-1481-66-ledningsevnestrømningscelle. The conductivity of the liquid is measured using a Cole-Parmer model J-1481-60 conductivity meter 20 equipped with a model J-1481-66 conductivity flow cell. Dernæst reverseres polariteten af voltmeteret, og den udstrømmende væske ledes tilbage gennem filterholderen under anvendelse af en trykdifference på ca. Next, the reversed polarity of the voltmeter, and the effluent is fed back through the filter holder using a differential pressure of about 1143 mm vandsøjle. 1143 mm water column. Som i det første tilfælde korrigeres det elektriske potentiale, der 25 måles under strømning, for cellepolarisation ved subtraktion derfra af det elektriske potentiale, der måles efter at strømningen er standset. As in the first case, the corrected electrical potential measured during flow 25, for cell polarization by subtracting from it the electrical potential measured after flow has stopped. Gennemsnitsværdien af de to korrigerede potentialer anvendes som strømningspotentialet. The average value of the two corrected potentials used as streaming potential.

Zeta-potentialet for mediet afledes af strømningspo-30 tentialet under anvendelse af den følgende relation (JT The zeta potential of the medium derived from strømningspo-30 tentialet using the following relation (JT

Davis et al.. Interfacial Phenomena, Academic Press, New York, 1963) : 4 7T^ Davis et al .. Interfacial Phenomena, Academic Press, New York, 1963): 4 7T ^

Zeta-potentiale = - * Εςλ 35 DP . Zeta potential = - * Εςλ 35 DP.

hvor n er viskositeten af den strømmende opløsning, D er wherein n is the viscosity of the flowing solution, D is

DK 175916 B1 I In DK 175916 B1

dens dielektricitetskonstant, λ er dens ledningsevne, Eg er I its dielectric constant, λ is its conductivity, Eg is the In

strømningspotentialet, og P er tryktabet over prøven under H streaming potential and P is the pressure drop across the sample during the H

strømningsperioden. flow period. Ved disse forsøg er størrelsen 4 irn/DP H In these experiments, the size 4 IRN / DP H

= 0,800. = 0.800. I IN

5 (K) Tangentiel strømningsfiltrering: Som benyttet i I 5 (K) Tangential flow filtration: As used in the I

nærværende beskrivelse refererer tangentiel strømningsfil- H herein, the tangential strømningsfil- H

trering til passage eller cirkulation af et biologisk fluidum H filtration for passing or circulating a biological fluid H

på en generelt parallel eller tangentiel måde i forhold til I in a generally parallel or tangential manner relative to I

overfladen af separationsmediet. the surface of the separation medium. H H

10 I de her omhandlede apparater eller organer og ved H 10 in the present apparatus or means and by H

fremgangsmåderne ifølge opfindelsen udføres leucocyt-fjemel- I the methods of the invention, the leucocyte In fjemel-

se fra et biologisk fluidum, f.eks. view from a biological fluid, for example. PRC eller PRP, på det be- PRC or PRP, to confirm the

handlingstidpunkt, der i USA i almindelighed ligger inden I Time of action, which in the United States generally lies within the

for ca. about 6-8 timer fra det tidspunkt, på hvilket blodet aftap- H 6-8 hours from the time at which the blood sump H

15 pes. 15 pes. Når således et biologisk fluidum overføres fra den pose, I Thus, when a biological fluid is transferred from the bag, In

i hvilken den er indeholdt, fjernes leucocyter af det egnede H in which it is contained, leucocytes are removed by the appropriate H

porøse medium, og leucocytfattigt biologisk fluidum opsamles . porous medium, and leucocytfattigt biological fluid is collected. I IN

i satellitposen. in the satellite bag. I overensstemmelse med opfindelsen til- H In accordance with the invention, to-H

vejebringes der et system, i hvilket et biologisk fluidum H there is provided a system in which a biological fluid H

20 såsom helblod behandles til dannelse af PRP og PRC. 20 such as whole blood is processed to form PRP and PRC. PRP I PRP In

befries for leucocyter ved indskydning mellem blodopsam- I freed of leucocytes by interposing between blodopsam- In

lingsposen og en første satellitpose af mindst ét porøst I Ling bag and a first satellite bag of at least one porous I

medium til fjernelse af leucocyter fra PRP; medium for depleting leucocytes from PRP; PRP befries for I PRP is freed of the I

leucocyter ved indskydning mellem blodopsamlingsposen og en I leucocytes by interposing between the blood collection bag and an I

25 anden satellitpose af mindst ét porøst medium til fjernelse I 25 the second satellite bag of at least one porous medium for removing In

af leucocyter fra PRC. leucocytes from PRC. I IN

Der kan anvendes et centrifugeringssystem, i hvilket I There may be used a centrifugation system in which the I

den ene eller begge af de indskudte leucocyt-fjernelses- I one or both of the interposer leucocyte removal In

filtersammensætninger er kooperativt anbragt sammen med en I Filter compositions are cooperatively arranged with an I

30 centrifugekurv på en sådan måde, at filtersammensætningen, 30 centrifuge basket in such a way that the filter assembly,

det porøse medium i filtersammensætningen og blodposerne H the porous medium in the filter assembly and the blood bags H

ikke beskadiges af de særdeles store kræfter, der frembringes H not damaged by the extremely high forces generated H

under centrifugeringsprocessen. during extraction process. H H

Fremgangsmåder og systemer ifølge opfindelsen kan H Methods and systems of the invention can be H

35 også omfatte et barrieremedium for røde blodlegemer, der H 35 also comprise a barrier medium for red blood cells that H

tillader passagen af én bestanddel af det biologiske fluidum, H allow the passage of one component of the biological fluid, H

DK 175916 B1 19 men hindrer passagen af en anden bestanddel gennem mediet, hvorved man eliminerer behovet for kontinuerlig overvågning af en operatør og forøger den effektivitet, med hvilken et biologisk fluidum, f.eks. DK 175916 B1 19 but prevents the passage of a second component through the medium, thereby eliminating the need for continuous monitoring of an operator and increases the efficiency with which a biological fluid, for example. helblod, opdeles i en eller flere 5 bestanddele. whole blood, divided into one or more components 5.

Desuden kan fremgangsmåder og systemer ifølge opfindelsen omfatte et gasudløb, der tillader gas, der kan være til stede i systemet, at passere ud af dette. In addition, the methods and systems of the invention include a gas outlet that allows gas that may be present in the system, to pass out of this.

Fremgangsmåder og systemer ifølge opfindelsen kan 10 også omfatte et gasindtag, der tillader indførsel af gas i systemet til udvinding af et biologisk fluidum, der kan indesluttes eller bibeholdes under behandling. Methods and systems of the invention may also 10 include a gas inlet to permit the entry of gas into the system to recover a biological fluid that may be entrapped or retained during processing.

Opfindelsen omfatter også behandlingen af et biologisk fluidum til uden centrifugering at adskille mindst én be-15 standdel fra det biologiske fluidum, f.eks. The invention also includes the treatment of a biological fluid to non-centrifugal separating at least one constituent BE-15 from the biological fluid, for example. behandling af PRP til opnåelse af plasma og PC, eller adskillelse af plasma fra helblod. treating PRP to obtain plasma and PC, or separating plasma from whole blood. Fremgangsmåder og organer eller apparater ifølge opfindelsen indebærer anvendelse af et separationsmedium, der tillader passagen af én bestanddel af det biologiske 20 fluidum, f.eks. Methods and means or device according to the invention involves the use of a separation medium that allows the passage of one component of the biological fluid 20, for example. plasma, men hindrer passage af andre bestanddele, f.eks. plasma, but prevents passage of other ingredients, for example. blodplader eller røde blodlegemer, gennem mediet, hvorved man eliminerer behovet for "hard-spin"-centrifugering som et behandlingstrin. platelets or red blood cells, through the medium, thereby eliminating the need for "hard-spin" centrifugation as a processing step. Tangentiel strømning af et biologisk fluidum parallelt med opstrøms-overfladen af sepa-25 rationsmediet tillader passagen af plasma gennem mediet, idet tendensen for cellulære bestanddele eller blodplader til at vedhænge ved mediets overflade reduceres, hvorved der bidrages til hindring af passage af blodplader gennem separationsmediet. Tangential flow of a biological fluid parallel to the upstream surface of SEPA 25 rationsmediet allow the passage of plasma through the medium, with the tendency for cellular components or platelets to append at the surface of the medium is reduced, thereby contributing to the prevention of passage of platelets through the separation medium. De hydrodynamiske forhold for strømning paral-30 lelt til en overflade antages faktisk at være således, at under strømning parallelt med overfladen udvikler blodplader et spin, der bevirker, at de kan udvindes fra overfladen. The hydrodynamics of flow parallelogram 30 lelt to a surface believed actually to be such that during flow parallel to the surface platelets develop a spin which causes them to be extracted from the surface.

På tegningen viser fig. In the drawings Fig. 1 en udførelsesform for et behandlingssystem 35 for et biologisk fluidum ifølge opfindelsen, i hvilket biologisk fluidum adskilles i bestanddele ved centrifugesepara- 20 1 One embodiment of a processing system 35 for a biological fluid according to the invention, in which the biological fluid is separated into components by centrifugesepara- 20

DK 175916 B1 I In DK 175916 B1

c ion. c ion. I IN

Fig. FIG. 2 viser en anden udførelsesfortn for et behand- I 2 shows a second udførelsesfortn for a treatment in

lingssystem for et biologisk fluidum ifølge opfindelsen, om- H Leveling system for a biological fluid according to the invention, rebuilding H

fattende et adskillelsesorgan uden centrifugering. comprising a separation body without centrifugation. I IN

5 Fig- 3 viser en udførelsesform for opfindelsen, der I 5 Fig- 3 shows an embodiment of the invention, the I

omfatter et gasindtag og et gasudtag. includes a gas inlet and a gas outlet. H H

Fig. FIG. 4 er et eksploderet perspektivbillede af en I 4 is an exploded perspective view of an I

udførelsesform for en filtersammensætning, en centrifugekurv H embodiment of a filter assembly, a centrifuge basket H

og en holder til passende anbringelse af filtersammensætnin- I and a holder for suitably positioning the filtersammensætnin- In

10 gen på kurven. 10 gene on the curve. H H

Fig. FIG. 5 viser et sidebillede af en udførelsesform for H 5 shows a side view of an embodiment of the H

opfindelsen. invention. H H

Fig. FIG. 6 viser et tværsnit af en udførelsesform for H 6 shows a cross section of an embodiment of the H

opfindelsen udvisende den første fluidumstrømningsvej i et H the invention showing the first fluid flow path in an H

15 separationsorgan ifølge opfindelsen. 15 separation device according to the invention. H H

Fig. FIG. 7 viser et snit i fig. 7 shows a section of Fig. 6 langs linien AA. 6 along the line AA. I IN

Fig. FIG. 8 viser et snit i fig. 8 shows a section of Fig. 6 langs linien BB. 6 along the line BB. I IN

Fig. FIG. 9 viser et tværsnit af en udførelsesform for I 9 shows a cross section of an embodiment of the I

opfindelsen udvisende den anden fluidumstrømningsvej i et I the invention showing the second fluid flow path in an I

20 separationsorgan ifølge opfindelsen. 20 separation device according to the invention. H H

Fig. FIG. 10 viser et snit i fig. 10 is a sectional view of Fig. 9 langs linien CC. 9 along the line CC. I IN

Fig. FIG. li viser et snit i fig. li shows a section of Fig. 9 langs linien DD. 9 along the line DD.

Et opsamlings- og behandlingsorgan for et biologisk I A pick-up and processing means for a biological In

fluidum, fortrinsvis blod, omfatter en første beholder og I fluid, preferably blood, comprising a first container and the In

25 en anden beholder samt en ledning, der indbyrdes forbinder I 25 a second container and a conduit interconnecting the I

den første beholder med den anden beholder, og mindst én I the first container with the second container, and at least one

tredje beholder og en ledning, der indbyrdes forbinder den H third container and a conduit interconnecting the H

første beholder med den tredje beholder, idet der indskudt I first container with the third container, being inserted into

mellem den første beholder og en anden beholder forefindes I between the first container and a second container is present in the

30 mindst ét første porøst medium, idet der indskudt mellem 30 at least one first porous medium being interposed between

den første og den tredje beholder forefindes mindst ét andet I the first and the third container, at least one second I

porøst medium. porous medium. Det første porøse medium kan være et leucocyt- I The first porous medium may be a leukocyte In

fjernelsesmedium, et barrieremedium for røde blodlegemer, I removal medium, a barrier medium for red blood cells, In

en sammensætning omfattende et leucocyt-fjernelsesmedium og I a composition comprising a leucocyte depletion medium and in

35 et barrieremedium for røde blodlegemer eller kombinationer I 35 a barrier medium for red blood cells, or combinations I

deraf. thereof. Det andet porøse medium kan være et leucocyt-fjernel- I The second porous medium may be a leucocyte removal In

DK 175916 B1 21 sesmedium, der om ønsket kan omfatte et mikroaggregat-filter-element og/eller et gel-forfilterelement. DK 175916 B1 sesmedium 21, if desired, may comprise a mikroaggregat filter element and / or a gel-forfilterelement. Som vist nærmere i det følgende kan sammensætningen også omfatte yderligere beholdere, porøse medier og ledninger, der indbyrdes for-5 binder beholderne og porøse medier. As shown in more detail below, the composition may also include additional containers, porous media, and conduits interconnecting the tie-5 containers and porous media.

Blodopsamlings- og -behandlingssammensætningen kan omfatte beholdere, der er indbyrdes forbundne med en ledning, og et porøst medium indskudt i ledningen til fjernelse af leucocyter fra PRC, hvor det porøse medium har en CWST-værdi 10 større end ca. Blood collection and processing assembly comprises containers interconnected with a conduit, and a porous medium interposed in the conduit for depleting leucocytes from PRC wherein the porous medium has a CWST greater than about 10 53 dyn/cm. 53 dynes / cm.

Blodopsamlings- og -behandlingssammensætningen kan omfatte beholdere indbyrdes forbundet med en ledning og et porøst medium indskudt i ledningen til fjernelse af leucocyter fra PRP, hvor det porøse medium har en CWST-værdi større 15 end ca. Blood collection and processing assembly comprises containers interconnected with a conduit and a porous medium interposed in the conduit for depleting leucocytes from PRP wherein the porous medium has a CWST greater than about 15 70 dyn/cm. 70 dynes / cm.

Et behandlingssystem for et biologisk fluidum omfatter en første beholder, et første porøst medium indeholdende et barrieremedium for røde blodlegemer, der står i forbindelse med den første beholder, og definerer en første 20 strømningsvej, samt et andet porøst medium omfattende et leucocyt-fjernelsesmedium, der står i forbindelse med den første beholder og definerer en anden strømningsvej. A processing system for a biological fluid comprising a first container to a first porous medium comprising a barrier medium for red blood cells, which is in communication with the first container, and defining a first 20 flow path, and a second porous medium comprising a leucocyte depletion medium, communicating with the first container and defining a second flow path. Som vist nærmere i det følgende kan systemet også omfatte yderligere beholdere, strømningsveje og porøse medier. As shown in more detail below, the system may also include additional containers, flow paths, and porous media.

25 Ved en fremgangsmåde til opsamling og behandling af blod opsamler man helblod i en beholder, centrifugerer helblodet, leder det ovenstående lag af det centrifugerede blod gennem et første porøst medium, idet det første porøse medium indeholder mindst ét leucocyt-fjernelsesmedium, et 30 barrieremedium for røde blodlegemer og et kombineret leucocyt-f jernelses-barrieremedium for røde blodlegemer, hvorpå sedimentlaget af det centrifugerede blod ledes gennem et andet porøst medium, hvor dette andet porøse medium indeholder et leucocyt-fjernelsesmedium. 25 In a method for collecting and processing blood comprising collecting whole blood in a container, centrifuging the whole blood, passing the supernatant layer of the centrifuged blood through a first porous medium, the first porous medium comprising at least one leucocyte depletion medium, a 30 barrier medium red blood cells and a combined leucocyte f jernelses cell barrier medium for red blood cells, passing the sediment layer of the centrifuged blood through a second porous medium, where the second porous medium comprising a leucocyte depletion medium.

35 En fremgangsmåde til behandling af et biologisk flui dum omfatter udpresning af et biologisk fluidum fra en første 35 A method of treating a biological UI dumb comprising expressing a biological fluid from a first

DK 175916 B1 I In DK 175916 B1

beholder til et første porøst medium indeholdende et bar- H container to a first porous medium comprising a bar- H

rieremedium for røde blodlegemer, og udpresning af et biolo- I arteries medium for red blood cells, and the pressing of a bio- In

gisk fluidum fra den første beholder til et andet porøst me- H cally fluid from the first container to a second porous metal H

dium. dium. Som vist nærmere i det følgende kan metoden også om- H As shown in more detail below, the method can also be converted H

5 fatte behandling af fluidet gennem yderligere beholdere, ad I 5 summarize the treatment of the fluid through additional containers, the I

yderligere strømningsveje og med yderligere porøse medier. further flow paths, and a further porous media. H H

Et eksempel på et opsamlings- og behandlingsystem fl An example of an acquisition and processing system and others

for biologisk fluidum er vist på tegningen i fig. the biological fluid is shown in the drawing of Fig. 1. Behand- I 1. The treatment In

lingssystemet for biologisk fluidum betegnes generelt ved 10. H processing system for the biological fluid is indicated generally at 10. The H

10 Det kan omfatte en første beholder eller opsamlingspose 11, I 10, it may comprise a first container or collection bag 11, In

en nål eller kanyle 1 egnet til indførsel i donoren, en H a needle or cannula 1 is suitable for introduction into the donor, an H

eventuel barrieresammensætning for røde blodlegemer 12, en H any barrier composition of red blood cells 12, a H

første leucocyt-fjernelses-sammensætning 13, en anden be- H first leucocyte depletion composition 13, a second confirm H

holder (første satellitpose) 41, en eventuel fjerde beholder H holder (first satellite bag) 41, an optional fourth container H

15 (tredje satellitpose) 42, en anden leucocyt-fjemelsessammen- I 15 (third satellite bag) 42, a second leucocyte In fjemelsessammen-

sætning 17 og en tredje beholder (anden satellitpose) 18. I sentence 17 and a third container (second satellite bag) 18. In

Hver af sammensætningerne eller beholderne kan være i fly- H Each of the compositions or containers may be in liquid H

dende forbindelse gennem rør, fortrinsvis bøjelige rør 20, H connecting connection through the pipes, preferably flexible tubing 20, H

21, 25, 26, 27 eller 28. Den første leucocyt-fjernelses- I 21, 25, 26, 27 or 28. The first leucocyte removal In

20 sammensætning omfatter fortrinsvis et porøst medium til at H Composition 20 preferably comprises a porous medium to H

lede PRP, og den anden leucocyt-fjernelses-sammensætning I directing the PRP, and the second leucocyte depletion composition I

omfatter fortrinsvis et porøst medium egnet til passage af H preferably comprises a porous medium suitable for passage of H

PRC. PRC. En forsegling, ventil, klemme eller overførselslukke I A seal, valve, clamp, or transfer close in

eller kanyle (ikke vist på tegningen) kan også være anbragt I or cannula (not shown in the drawings) can also be enclosed in

25 i eller på rørene eller i opsamlings- og/eller satellitposer- I 25 in or on the pipes or in the collection and / or satellitposer- In

ne. ne. Forseglingen eller forseglingerne åbnes, når fluidet skal H The seal or seals is opened when fluid is to be H

overføres mellem poser. transferred between bags. I IN

I et andet eksempel på en konfiguration er blodbe- H In another example of a configuration is blodbe- H

handlingssystemet vist i fig. treatment system shown in Fig. 2 det samme som det eksempel I 2 the same as the Example I

30 på et system, der er vist i fig. 30 on a system, shown in FIG. 1, men med den undtagelse, H 1, but with the exception that H

at delen af systemet nedstrøms for leucocyt-fjernelsessam- I that portion of the system downstream of leucocyte In fjernelsessam-

mensætningen 13 omfatter en separationssammensætning 14, H composition 13 comprises a separation composition 14, H

fortrinsvis en separationssammensætning uden centrifugering. Preferably, a separating composition without centrifugation. H H

I et andet eksempel på en konfiguration vist i fig. In another example of a configuration shown in Fig. H H

35 3 kan opfindelsen også omfatte mindst ét gasindtag 51, 53 I 35 3, the invention may also comprise at least one gas inlet 51, 53 In

og/eller mindst ét gasudtag 52, 54. Systemet vist i fig. and / or at least one gas outlets 52, 54. The system shown in Fig. 3 I 3 In

DK 175916 B1 23 · omfatter en første beholder eller opsamlingspose 11 i fluid forbindelse med en eventuel barrieresammensætning 12 for røde blodlegemer, et gasindtag 53, en leucocyt-fjernelses-sammensætning 13 og et gasudtag 54. Den første beholder 11 5 kan også være i fluid forbindelse med et gasindtag 51, et leucocyt-fjerneIses-organ 17 og et gasudtag 52. Som nærmere vist i det følgende kan sammensætningen også omfatte yderligere beholdere, strømningsveje og porøse medier. DK 175916 B1 23 · comprises a first container or collection bag 11 in fluid communication with an optional barrier composition 12 for red blood cells, a gas inlet 53, leucocyte depletion composition 13 and a gas outlet 54. The first container 11 5 may also be in fluid connection with a gas inlet 51, a leucocyte fjerneIses body 17 and a gas outlet 52. As shown in detail hereinafter, the composition may also include additional containers, flow paths, and porous media.

Ethvert antal og kombinationer af sammensætninger 10 eller organer, porøse medier, beholdere og ledninger er egnet. Any number and combinations of compositions or bodies 10, porous media, containers, and conduits are suitable. En fagmand på området vil forstå, at opfindelsen som her beskrevet kan omkonfigureres i forskellige kombinationer, der falder inden for opfindelsesomfanget. One skilled in the art will appreciate that the invention described herein may be reconfigured into different combinations, which fall within the invention scope.

Hver af komponenterne i sammensætningen eller ap-15 paratet skal herefter beskrives i nærmere enkeltheder. Each of the components in the composition or AP-PREPARATION 15 will now be described in more detail.

De beholdere, der anvendes i behandlingsapparatet for det biologiske fluidum, kan være konstrueret af ethvert materiale, der er foreneligt med et biologisk fluidum, f.eks. The containers used in the processing apparatus for the biological fluid, may be constructed of any material which is compatible with a biological fluid, for example. helblod eller en blodbe s tanddel, og er i stand til at modstå 20 en centrifugering og et steriliseringsmiljø. whole blood or blodbe s tooth part, and is capable of withstanding 20:01 centrifugation and sterilization environment. Et bredt udvalg af disse beholdere er allerede kendte i teknikken. A wide variety of these containers are already known in the art. Eksempelvis fremstilles blodopsamlings- og satellitposer typisk ud fra blødgjort polyvinylchlorid, f.eks. Prepared, for example blood collection and satellite bags are typically prepared from plasticized polyvinylchloride, for example. PVC blødgjort med dioctylphthalat, diethylhexylphthalat eller trioctyltrimel-25 litat. PVC plasticized with dioctylphthalate, diethylhexylphthalate, or trioctyltrimel-25 litat. Poserne kan også fremstilles ud fra polyolefin, poly-urethan, polyester og polycarbonat. The bags may also be prepared from polyolefin, polyurethane, polyester and polycarbonate.

Som her anvendt kan rørene være vilkårlige ledninger eller organer, der tilvejebringer fluid forbindelse mellem beholderne, og de er typisk fremstillet ud fra det samme 30 fleksible materiale, som anvendes til beholderne, fortrinsvis blødgjort PVC. As used herein, the pipes can be any conduits or means which provides fluid communication between the containers, and are typically made from the same flexible material 30, which is used for the containers, preferably plasticized PVC. Rørene kan strække sig ind i det indre af beholderne og kan f.eks. The tubes may extend into the interior of the containers and may, for example. anvendes som en sifon. used as a siphon. Der kan være et antal rør, der tilvejebringer fluid forbindelse til enhver individuel beholder, og rørene kan være orienteret 35 på forskellige måder. There may be a number of tubes providing fluid communication to any individual container, and the tubes 35 may be oriented in different ways. Eksempelvis kan der være mindst to rør orienteret ved toppen af opsamlingsposen eller ved bunden For example, there may be at least two tubes oriented at the top of the collection bag, or at the bottom

DK 175916 B1 I In DK 175916 B1

24 I In 24

af posen, eller der kan forefindes et rør ved hver ende af I of the bag, or there may be provided a pipe at each end of I

posen. bag. I IN

Desuden kan rørene, apparatdelene, porøse medier og I In addition, the tubes, appliance parts, porous media, and I

beholdere være orienteret til at definere forskellige strøm- I containers may be oriented to define different current I

5 ningsveje. 5-making paths. Når der f.eks. When, for example. behandles helblod, kan PRP strømme treated whole blood, PRP may flow

langs en første strømningsvej, f.eks. along a first flow path, for example. gennem barrieresamlin- I In through barrieresamlin-

gen for røde blodlegemer, såfremt en sådan er til stede, en I gene for red blood cells, if such is present, an I

PRP-leucocyt-fjernelsessammensætning og ind i en satellit- I The PRP leucocyte depletion assembly, and into a satellite in

pose, f.eks. bag, for example. en anden beholder. a second container. På lignende måde kan PRC I Similarly, the PRC In

10 strømme langs en anden strømningsbane, f.eks. 10 flow along a second flow path, for example. gennem PRC- I In through the PRC

leucocyt-fjernelsesorganet og ind i en satellitpose, f.eks I leukocyte removal means and into a satellite bag, for example, in

en tredje beholder. a third container. Eftersom uafhængige strømningsbaner kan I Since independent flow paths can

være til stede, kan biologiske fluida, f.eks. be present, biological fluids, for example. PRP og PRC, I PRP and PRC, IN

strømme samtidigt eller sekventielt. currents simultaneously or sequentially. I IN

15 En forsegling, ventil, klemme, et overføringslukke H 15 A seal, valve, clamp, transfer a closure H

eller lignende er typisk lokaliseret i eller på røret. or the like is typically located in or on the tube. Det H This H

er hensigten, at opfindelsen ikke skal begrænses af den type materiale, der anvendes til konstruktion af beholderne, eller den ledning, der forbinder beholderne. is intended that the invention not be limited by the type of material used to construct the containers or the conduit which connects the containers.

20 Sammensætningen af de forskellige porøse medier vil I 20 The composition of the various porous media will

afhænge delvis af den ønskede funktion, f.eks. depend in part on the desired function, for example. blokering af I blocking of I

røde blodlegemer eller leucocytfjernelse. red blood cells or leucocyte depletion. En foretrukken a preferred

sammensætning af de forskellige porøse medier er en måtte I composition of the various porous media is a mat In

eller et væv sammensat af fibre, der fortrinsvis er ter- H or a tissue composed of fibers that preferably are ter- H

25 moplastiske. 25 moplastiske. Fibrene i de porøse medier kan omfatte vilkår- I The fibers of the porous media may comprise arbitrary In

lige fibre, der er forenelige med biologisk fluidum, og de I fibers, which are compatible with biological fluid, and the In

kan være enten naturlige eller syntetiske fibre. may be either natural or synthetic fibers. Ifølge According to

opfindelsen er fibrene fortrinsvis behandlet eller modifi- I the invention, the fibers are preferably treated or modified in

ceret til opnåelse eller forøgelse af CWST-værdien. ed to obtain or increase the CWST. Eksem- I By way I

30 pelvis kan fibrene være overflademodificeret til forøgelse I The pelvis 30, the fibers may be surface modified to increase I

af den kritiske fugtede overfladespænding (CWST) for fibrene. of the critical wetting surface tension (CWST) of the fibers. I IN

Eksempelvis har de behandlede eller ubehandlede fibre, der I For example, the treated or untreated fibers, in that

anvendes i PRC-porøst medium, fortrinsvis en CWST-værdi I used in the PRC porous medium preferably have a CWST in

over ca. over about 53 dyn/cm, og for PRP-porøst medium over ca. 53 dyne / cm, and for the PRP porous medium, above about 70 I In 70

35 dyn/cm. 35 dynes / cm. Fibrene kan også være bundet, sammensmeltet eller I The fibers may also be bonded, fused, or I

på anden måde fikseret til hverandre, eller de kan være I otherwise fixed to each other, or they may be in the

DK 175916 B1 25 mekanisk sammensnoet. DK 175916 B1 25 mechanically entwined. Andre porøse medier, f.eks. Other porous media, for example. åbentcellet skumplast, der er overflademodificeret som ovenfor angivet, kan anvendes på tilsvarende måde. open-cell foam plastic, which is surface modified as noted above, may be used in a corresponding manner.

Medens de porøse medier kan fremstilles ud fra ethvert 5 materiale, der er foreneligt med biologisk fluidum, dikterer praktiske overvejelser, at man først bør overveje anvendelsen af kommercielt tilgængelige materialer. While the porous media can be made from any material 5 that is compatible with biological fluid, practical considerations dictate that one should first consider the use of commercially available materials. De porøse medier kan fortrinsvis dannes ud fra f.eks. The porous media may preferably be formed from, for example. enhver syntetisk polymer, der er i stand til at danne fibre og tjene som et sub-10 strat for podning. any synthetic polymer capable of forming fibers and serve as a sub-10 substrate for grafting. Fortrinsvis bør den polymere være i stand til at reagere med mindst én ethylenisk monomer under indflydelse af ioniserende stråling, uden at matrixen signifikant eller ekscessivt påvirkes i uønsket retning af strålingen. Preferably, the polymer should be capable of reacting with at least one ethylenic monomer under the influence of ionizing radiation without the matrix being significantly or ekscessivt adversely affected by the radiation. Egnede polymere til anvendelse som substratet omfatter, 15 men er ikke begrænset til polyolefiner, polyestere, polyamider, polysulfoner, acrylharpikser, polyacrylonitriler, poly-aramider, polyarylenoxider og -sulfider, samt polymere og copolymere fremstillet ud fra halogenerede definer og umættede nitriler. Suitable polymers for use as the substrate include, but are not 15 limited to, polyolefins, polyesters, polyamides, polysulfones, acrylics, polyacrylonitriles, poly-aramids, polyarylene oxides and sulfides, and polymers and copolymers made from halogenated refine and unsaturated nitriles. Eksempler omfatter, men er ikke begrænset 20 til polyvinylidenfluorid, polyethylen, polypropylen, celluloseacetat og nylon 6 og 66. Foretrukne polymere er polyole-finer, polyestere og polyamider. Examples include, but are not limited 20 to polyvinylidene fluoride, polyethylene, polypropylene, cellulose acetate, and Nylon 6 and 66. Preferred polymers are polyolefines, polyesters and polyamides. Den mest foretrukne polymer er polybutylenterephthalat (PBT). The most preferred polymer is polybutylene terephthalate (PBT).

Overfladeegenskaber for en fiber kan forblive umodi-25 ficerede eller kan modificeres ved et antal metoder, f.eks. Surface properties of a fiber may remain umodi 25-fied or may be modified by a number of methods, for example. ved kemisk reaktion omfattende våd eller tør oxidation, ved overtrækning af overfladen ved afsætning af en polymer derpå eller ved podningsreaktioner, ved hvilke substratet eller fiberoverfladen aktiveres forud for eller under befugtning 30 af fiberoverfladen med en monomeropløsning ved udsættelse for en energikilde såsom varme, en Van der Graff-generator, ultraviolet lys eller for andre former for betråling, eller ved udsættelse af fibrene for gasplasma-behandling, En fo-retrukken metode er en podningsreaktion under anvendelse 35 af gamma-stråling, f.eks. by chemical reaction including wet or dry oxidation, by coating the surface by depositing a polymer thereon or by grafting reactions in which the substrate or fiber surface is activated prior to or during wetting 30 of the fiber surface by a monomer solution by exposure to an energy source such as heat, a Van there Graff generator, ultraviolet light or other forms of betråling, or by subjecting the fibers to gas plasma treatment, an Fo retrukken method is a grafting reaction using gamma-35 of radiation, for example. fra en cobaltkilde. from a cobalt source. i in

Ved et eksempel på en bestrålings-podningsteknik In an exemplary radiation grafting technique

DK 175916 B1 I In DK 175916 B1

anvendes der mindst én af en række monomere, der hver in- H , at least one of a variety of monomers each in-H

deholder en ethylen- eller acrylisk del og en anden gruppe, containing an ethylene or acrylic moiety and a second group,

der foretrækkes at være en hydrofil gruppe, f.eks. which is preferred to be a hydrophilic group, for example. -COOH H -COOH H

eller -OH. or -OH. Podning af det fibrøse medium kan også udføres I Grafting of the fibrous medium may also be conducted in

5 med forbindelser indeholdende en ethylenisk umættet gruppe, I 5 with compounds containing an ethylenically unsaturated group in

f.eks. eg. en acrylisk del, kombineret med en hydroxylgruppe, I an acrylic moiety combined with a hydroxyl group, In

fortrinsvis monomere såsom hydroxyethylmethacrylat (HEMA) fl Preferably, monomers such as hydroxyethyl methacrylate (HEMA) fl

eller acrylsyre. or acrylic acid. Forbindelserne indeholdende en ethylenisk H The compounds containing an ethylenically H

umættet gruppe kan kombineres med en anden monomer, såsom H unsaturated group may be combined with another monomer, such as H

10 methylacrylat (MA), methylmethacrylat (MMA) eller methacryl- I 10 methyl acrylate (MA), methyl methacrylate (MMA) or methacrylic In

syre (MAA). acid (MAA). MA eller MAA inkorporeres fortrinsvis i det I MA or MAA is preferably incorporated into the I

porøse medium, der anvendes til behandling af PRC, og MAA I porous medium used to treat PRC, and MAA In

inkorporeres fortrinsvis i det porøse medium, der anvendes I is preferably incorporated into the porous medium used in the

til at behandle PRP. to treat the PRP. Fortrinsvis kan vægtforholdet mellem I Preferably, the weight ratio of I

15 MAA og HEMA-monomer i den modificerende blanding ligge mellem I 15 MAA and HEMA-monomer in the modifying mixture may be between I

ca. ca. 0,01:1 og ca. 0.01: 1 and about 0,5:1, og fortrinsvis kan vægtforholdet I 0.5: 1, and preferably, the weight ratio I

mellem MA eller MMA og HEMA-monomer i den modificerende I between the MA or MMA to HEMA monomer in the modifying In

blanding ligge mellem ca. mixture will be from about 0,01:1 og ca. 0.01: 1 and about 0,4:1. 0.4: 1st Anvendelse I use In

af HEMA bidrager til en meget høj CWST-værdi. HEMA contributes to a very high CWST. Analoge med I In analogous to

20 lignende funktionelle karakteristika kan også anvendes til I 20 similar functional characteristics may also be used in

at modificere fibrenes overfladeegenskaber. modifying the surface characteristics of fibers. I IN

Det er blevet iagttaget, at porøse medier, der er I It has been observed that porous media in

overfladebehandlet under anvendelse af nogle podemonomere I surface treated using some grafting monomers in

eller kombinationer af monomere, opfører sig forskelligt I or combinations of monomers, behave differently in

25 med hensyn til forskellen mellem overfladespændingen af den I 25 in terms of the difference between the surface tension of the In

væske, der absorberes, og overfladespændingen af den væske, I liquid which is absorbed and the surface tension of the liquid in

der ikke absorberes, når CWST-bestemmes. which is not absorbed when the CWST-determined. Denne forskel kan I This difference can

variere fra mindre end 3 til så meget som 20 eller flere I vary from less than 3 to as much as 20 or more In

dyn/cm. dynes / cm. Fortrinsvis har mediet en forskel mellem de absor- I Preferably, the medium is a difference between the absorbance I

30 berede og ikke-absorberede værdier på ca. 30 and prepare the non-absorbed values ​​of about 5 eller færre I 5 or fewer I

dyn/cm. dynes / cm. Dette valg afspejler den større præcision, med hvil- I This choice reflects the greater precision with hvil- In

ken CWST-værdien kan reguleres, når der vælges snævrere I Ken CWST can be controlled when narrower is selected in

forskelle, om end medier med videre forskelle også kan an- I differences, although media on differences also can AN- In

vendes. reversed. Anvendelsen af den mindre forskel foretrækkes til I The use of the smaller difference is preferable to I

35 forbedring af produktkvalitetskontrol. 35 the improvement of product quality control. I IN

Bestrålingspodning kan forøge fiber-til-fiber-binding H Bestrålingspodning may increase fiber-to-fiber H-bond

DK 175916 B1 27 i et fibermedium. DK 175 916 B1 in a 27 fiber medium. Således kan et fibermedium, der udviser lille eller ingen fiber-til-fiber-binding i en ubehandlet tilstand, udvise signifikant fiber-til-fiber-binding, efter at fibrene er blevet bestrålingspodede til forøgelse af 5 mediets CWST-værdi. Thus, a fibrous medium which exhibits little or no fiber-to-fiber bonding in an untreated state may exhibit significant fiber-to-fiber bonding after the fibers have been radiation grafted to increase the 5 CWST of the medium.

For de porøse medier til anvendelse i forbindelse med et biologisk fluidum, f.eks. For the porous media for use in connection with a biological fluid, for example. PRP, ligger et foretrukkent område for CWST for fiberen fortrinsvis over ca. PRP, is a preferred range for the CWST of the fiber is preferably above about 70 dyn/cm, typisk fra ca. 70 dynes / cm, typically from about 70 til 115 dyn/cm, idet et mere foretrukkent 10 område ligger fra 90-100 dyn/cm og et specielt foretrukkent område ligger fra 93-97 dyn/cm. 70 to 115 dyne / cm, with a more preferred 10 range is from 90 to 100 dyne / cm and a particularly preferred range of 93 to 97 dyne / cm. Et foretrukkent område for zeta-potentialet (ved pH-værdien '7,3 for plasma) er fra ca. A preferred range for the zeta potential (at the pH '7.3 for the plasma) is from about

-3 til ca. To about -3 -30 millivolt, et foretrukkent område ligger fra ca. -30 millivolts, a more preferred range is from about -7 til ca. -7 to about -20 millivolt og et specielt foretrukkent 15 område ligger fra ca. -20 millivolts, and a particularly preferred region 15 is from about -10 til ca. -10 to ca. -14 millivolt. -14 millivolts.

I de pakkede røde blodlegemer såvel som i helblod er de røde blodlegemer suspenderet i blodplasma, der har en overfladespænding på ca. In the packed red blood cells as well as in whole blood, the red blood cells suspended in blood plasma, which has a surface tension of about 73 dyn/cm. 73 dynes / cm. Til fjernelse af leuco-cytindholdet af PRC er en CWST-værdi større end ca. For the removal of leuco cytindholdet of PRC has a CWST greater than about 53 dyn/cm 20 ønskelig. 53 dyne / cm 20 desirable. CWST-værdien kan typisk ligge over fra ca. CWST may typically be above from about 53 til ca. To about 53 115 dyn/cm, men opfindelsen skal ikke begrænses herved. 115 dynes / cm, but the invention should not be limited thereby.

En mere foretrukken CWST-værdi ligger over ca. A more preferable CWST is above about 60 dyn/cm, og en endnu mere foretrukken CWST-værdi ligger fra ca. 60 dyne / cm, and a still more preferable CWST is from about 62 dyn/cm til mindre end ca. 62 dynes / cm to less than about 90 dyn/cm. 90 dynes / cm.

25 Om ønsket kan strømningshastigheden af biologisk 25 If desired, the flow rate of the biologically

fluidum gennem filteret reguleres til opnåelse af en total strømningsperiode på fra ca. fluid through the filter is regulated to obtain a total flow period of from about 10 til 40 minutter ved udvælgelse af passende elementdiameter, elementtykkeIse, fiberdiameter og massefylde, og/eller ved variation af diameteren I 10 to 40 minutes by selecting the appropriate element diameter, elementtykkeIse, fiber diameter, and density, and / or by varying the diameter of the

30 af røret enten opstrøms eller nedstrøms fra filteret, eller | 30 of the tube either upstream or downstream from the filter, or | både op- og nedstrøms. both up and downstream. Ved disse strømningshastigheder kan der opnås en leucocyt-fjernelseseffektivitet, der overstiger 99,9%. At these flow rates can obtain a leucocyte depletion efficiency in excess of 99.9%. Såfremt PRP er det biologiske fluidum, der behandles, kan disse effektivitetsniveauer resultere i et PC-produkt 35 med mindre end ca. If PRP is the biological fluid being processed, these levels of efficiency result in a PC product with less than 35 about 0,1 x 10e leucocyter pr. 0.1 x 10E leucocytes per. enhed PC, sammenlignet med målsætningen på mindre end 1 x 106. PC unit, compared with the target of less than 1 x 106th

DK 175916 B1 I In DK 175916 B1

Det leucocyt-fjernende PRC-porøse medium skal primært H The leukocyte-removing PRC porous medium is primarily H

anvendes i forbindelse med PRC opnået fra donorblod inden H used in connection with PRC obtained from donated blood within H

for ca. about 8 timer fra det tidspunkt, på hvilket blodet er H 8 hours from the time at which the blood is H

aftappet. bottled. Det kan også anvendes til at filtrere PRC, der I It may also be used to filter PRC which

5 har været opbevaret ved 4°C i op til flere uger, men eftersom H 5 have been stored at 4 ° C for up to several weeks, but, since H

risikoen for tilstopning under filtrering forøges med op- H the risk of clogging during filtration increases with the up H

bevaringstiden, kan risikoen f.eks. Conservation time, the risk for example. formindskes under anven- H decreases during application H

delse af for-filtre, der går forud for de her beskrevne H MEMORANDUM of the filters, which precedes the described H

medier. media. H H

10 Et her omhandlet PRC-porøst medium kan fremstilles H 10 a present PRC porous medium can be prepared H

til at have et bredt område af effektiviteter til leucocyt- H to have a wide range of efficiencies for leukocyte H

fjernelse. removal. Hvis det porøse medium er sammensat af 2,6 μιη- H If the porous medium is composed of 2.6 μιη- H

fibre og vejer ca. fibers and weighs about H H

15 p-^27,98 - gram (3) I 15 p- ^ 27.98 - gram (3)

hvor p = fibermassefylde i gram/cm·3 H wherein p = fiber density in grams / cm · 3 H

©9 V — hulrumsrumfang i %, © 9 V - cavity volume in%

20 kan, når det anvendes til leucocytf jernelse i PRC, logaritmen H 20, when it is used for leucocytf iron presence in the PRC, the log H

til effektiviteten, defineret som forholdet mellem den ind- H of efficacy, defined as the ratio of the input H

strømmende leucocytkoncentration til den udstrømmende leu- H flowing leucocyte concentration to the effluent Leu- H

cocytkoncentration, beregnes ud fra formlen H cocytkoncentration, determined by the formula H

25 Log effektivitet = 25,5 · Il - —— ) (4) I 25 Sign efficiency = 25.5 · Il - -) (4)

V 100/ I 100 V / I

Til de fleste anvendelser er det ønskeligt at holde strøm- I For most applications, it is desirable to maintain the current I

ningstiden for en enhed af PRC gennem det porøse medium, I up time of a unit of PRC through the porous medium, I

30 når der anvendes tryk på fra ca. 30 when using pressure of from about 30 til 300 mm Hg, på mindre I 30 to 300 mm Hg of less In

end ca. than about 30-40 minutter. 30-40 minutes. Til opnåelse af denne strømningsha- H To achieve this The flow H

stighed bør apparaturet fortrinsvis være udformet til et H speed apparatus should preferably be formed to an H

strømningsareal på fra ca. the flow area of ​​from about 30 til 60 cm2. 30 to 60 cm 2. H H

Eksempelvis vil et 8,63 cm diameter (areal = 58,5 I For example, an 8.63 cm diameter (area = 58.5 I

35 cm2) porøst medium fremstillet under anvendelse af 7,7 g af I 35 cm2) porous medium made using 7.7 grams of I

2,6 //m-diameter, 1,38 g pr. 2.6 // m diameter, per 1.38 g. cm·3-massefylde-fiber med et hul- H · cm 3 density fiber with a hole H

rumsvolumen på 76,5% opfylde kravene til ligning (3) og I space volume of 76.5% meet the requirements of equation (3) and In

29 DK 175916 B1 dets leucocyt-fjernelseseffektivitet i overensstemmelse med ligning (4) vil være log 6. Hvis således den indstrømmende koncentration er 109 leucocyter/enhed, vil den udstrømmende koncentration være T§6 - 103 På tilsvarende måde, såfremt det porøse medium er 10 fremstillet med V = 88,2% under anvendelse af 2,6 μπι diameter-fibre med en massefylde på 1,38 g/cm3, vil vægten af det . 29 DK 175916 B1 its leucocyte depletion efficiency, in accordance with equation (4) would be log 6. Thus, if the influent concentration is 109 leucocytes / unit, the effluent concentration would be T§6 - 103 In a similar manner, if the porous medium is 10 is made with V = 88.2% using 2.6 μπι-diameter fibers having a density of 1.38 g / cm 3, the weight of it. porøse medium ifølge ligning (3) være følgende: 15 1,38-^27,98 - (29,2β X ffj2)! porous medium according to the equation (3) as follows: 15 1,38- 27.98 ^ - (X 29,2β ffj2)! = 3,0 gram og logaritmen til effektiviteten vil ifølge ligning (4) være følgende: 20 Log effektivitet = 25,5*^1 - = 3,0 = 3.0 gram and the log of the efficiency, according to equation (4) as follows: efficiency = 20 log 25.5 * ^ 1 - 3.0 =

Hvis således den indstrømmende leucocytkoncentration 25 er 109 pr. Thus, if the influent leucocyte concentration that is 25 per 109. enhed PRC, vil den udstrømmende koncentration være 109 c —3 = 10® pr. device PRC, the effluent concentration would be 109 -3 = C per 10®. enhed 30 Ligningerne (3) og (4) kan anvendes til et hulrums rumfang i området fra ca. Unit 30 The equations (3) and (4) can be used for a cavity volume in the range from about 73 til 88,5%, hvilket spænder over effektivitetsområdet fra ca. 73 to 88.5%, which spans the efficiency range from about log 3 til log 7. log 3 to log 7th

Ligningerne (3) og (4) giver særdeles nyttige retningslinier til udformning og opbygning af optimale eller 35 næsten optimale PRC-filtre, idet der kun kræves begrænsede forsøg. Equations (3) and (4) provide very useful guidelines for designing and building optimal or 35 almost optimal PRC filters, requiring only limited attempts. En person, der er bekendt med den pågældende teknik, vil imidlertid forstå, at afvigelser fra disse formler og modifikationer af de porøse medier kan foretages til frem- i A person familiar with the technique, however, will understand that deviations from these formulas and modifications to the porous media can be made to flow in

DK 175916 B1 I In DK 175916 B1

3° I 3 °

stilling af nyttige produkter. position of useful products. Eksempler på modifikationer I Examples of modifications in

og deres virkning på ydeevneegenskaberne af de porøse medier I and their effect on the performance properties of the porous media I

fremgår af det følgende: I set out below: In

DK 175916 B1 31 Ønskede filtereoenskaber Ændringer fra ligninger (3) og (4)_ DK 175916 B1 31 Preferred filtereoenskaber Changes from Equations (3) and (4) _

Forøget leucocyt-fjer- o Nedsæt fiberdiameter nelseseffektivitet o Forøg vægt af fiber 5 o Nedsæt hulrumsrumfang Increased leucocyte feathers- o Reduce fiber diameter formation efficiency o Increase weight of fiber o Reduce voids 5 volume

Formindsket sandsynlighed o Forøg filterelement-areal for tilstopning o Anvend for-filtrering 10 o Forøg hu1rumsrumfang Reduced probability o Increase filter element area for clogging o Apply filtering 10 o Increase hu1rumsrumfang

Formindsket indre "hold- o Nedsæt hu1rumsrumfang) up"-rumfang o Eliminér for-filtrering) o Anvend finere fiber 15 Reduced inner "attitude o Reduce hu1rumsrumfang) up" -rumfang o Eliminate for filtering) o Use finer fiber 15

Forøget strømningshastig- o Behandl blodet således, at hed af PRC PRC har lavere hæmatokrit; The flow rate increased o Process the blood such that the PRC was called the PRC has lower hematocrit; derved lavere viskositet o Anvend højere hovede ved 20 filtrering o Forøg filterareal med samtidig reduktion af tykkelse o Forøg filterelernent-hulrums-rumfang 25 thereby lower viscosity o Use higher head when filtering 20 o Increase filter area with concomitant reduction of thickness o Increase filterelernent-volume cavity 25

Modstandsdygtighed mod o Nedsæt element-hulrumsrumhøjere anvendt differentielt fang tryk o Anvend grovere fiber (på bekostning af reduceret 30 effektivitet) o Anvend fiber med højere modul Resistance to o Reduce element-hulrumsrumhøjere used differentially Fang pressure o Use coarser fiber (at the cost of reduced efficiency 30) o Use fiber with higher modulus

32 I 32

DK 175916 B1 I In DK 175916 B1

(1) Anvendelse af en for lille fiberdiameter kan resultere I (1) Use of too small a fiber diameter may result in

i kollaps af filterelementet ved normalt arbejds- I the collapse of the filter element at normal working In

differentialtryk. differential pressure. I IN

(2) Kan resultere i ekscessivt lange filtreringstider I (2) May result in ekscessivt long filtration times I

5 eller fuldstændig tilstopning forud for fuldendelsen I 5, or complete clogging prior to completion In

af en transfusion. of a transfusion. I IN

Barrieremedium for røde blodlegemer I The barrier medium for red blood cells in

Barrieresammensætninger for røde blodlegemer som I The barrier compositions of red blood cells as in

10 f.eks. 10 for example. er indskudt mellem blodopsamlingsposen og PRP-posen, I is interposed between the blood collection bag and the PRP bag, In

vil i almindelighed fjerne fra ca. will generally remove about 85-79% eller mere af de I 85 to 79% or more of the In

forekommende leucocyter, en fjernelsesgrad, der i givet I occurring leucocytes, the removal degree, where I

fald ikke vil være tilstrækkelig til konsekvent at opnå en I case will not be sufficient to consistently achieve In

restleucocytmængde på mindre end 10® leucocyter pr. restleucocytmængde less than 10® leucocytes per. enhed I unit in

15 PC. 15 PC. En principiel funktion af denne barrieresammensætning I A principal function of this barrier composition In

er imidlertid at fungere som en automatisk "ventil" under I however, is to act as an automatic "valve" during the I

dekanteringsprocessen ved øjeblikkelig standsning af strømmen I decantation process by instantly stopping the current I

af et biologisk fluidum, f.eks. a biological fluid, for example. det ovenstående lag, f.eks. the supernatant layer, for example. I IN

PRP, i det øjeblik, hvor røde blodlegemer kommer i kontakt PRP, in the moment when red blood cells come in contact

20 med porøse medier indeholdende det porøse medium. 20 with porous media containing the porous medium. Mekanismen I The mechanism in

ved denne ventil-lignende virkning er ikke godt forklaret, I in this valve-like action is not well explained, In

men den kan afspejle aggregeringen af de røde blodlegemer, I but it may reflect aggregation of the red blood cells, In

når de når den porøse overflade, idet de danner en barriere, I when they reach the porous surface, forming a barrier, I

der hindrer eller blokerer yderligere strømning af det oven- I which prevents or blocks further flow of the above-In

25 stående lag gennem det porøse medium. 25 below layer through the porous medium. I IN

Aggregering af røde blodlegemer ved kontakt med det I Aggregation of red cells on contact with the In

porøse filter synes at være relateret til CWST-værdien I porous filter appears to be related to the CWST In

og/eller til andre, mindre godt forståede overfladeegenskaber I and / or to other, less well understood surface characteristics in

for fibrene, der dannes ved den her beskrevne metode til I for the fibers formed by the method described herein to I

30 modifikation af fibrene. 30 the modification of the fibers. Denne teori for den foreslåede I This theory for the proposed In

mekanisme understøttes af eksistensen af filtre, der er i I mechanism is supported by the existence of filters that are in

stand til at udøve højeffektiv leucocyt-fjernelse fra suspen- I able to exert high efficiency leukocyte removal from the suspension I

sioner af røde blodlegemer fra mennesker, og som har pore- I suspensions of red blood cells from humans, and which have pore In

størrelser så små som 0,5 μτα, gennem hvilke røde blodlegemer I sizes as small as 0.5 μτα through which red blood cells in

35 passerer frit og fuldstændigt uden tilstopning, med påsat I 35 pass freely and completely with no clogging, with applied I

tryk af samme størrelsesorden som anvendt ifølge opfindel- I pressure of the same order as used according to the inventions I

33 DK 175916 B1 sen. 33 DK 175916 B1 late.

På den anden side vil de omhandlede filtre, der typisk har porediametre større end ca. On the other hand, these filters typically have pore diameters larger than about 0,5 μιη, brat standse strøm- ningen af røde blodlegemer, når det porøse medium bringes i 5 kontakt med de røde blodlegemer. 0.5 μιη, abruptly stop the power scheme of red blood cells when the porous medium 5 is brought into contact with the red blood cells. Dette antyder, at den ventil-lignende virkning ikke er relateret til eller forårsaget af porestørrelse eller af en filtreringsmekanisme. This suggests that the valve-like action is not related to or caused by pore size or by a filtration mechanism. Mekanismen for denne ventil-lignende virkning er ikke godt forstået, men den kan afspejle zeta-potentiale-relateret aggregering 10 af de røde blodlegemer, når de når filteroverfladen, idet de danner en barriere, der hindrer eller blokerer yderligere strømning af et biologisk fluidum indeholdende røde blodlegemer gennem det porøse medium. The mechanism of this valve-like action is not well understood, but it may reflect zeta potential-related aggregation 10 of the red cells as they reach the filter surface, forming a barrier which prevents or blocks further flow of a biological fluid containing red blood cells through the porous medium.

Filtersammensætningen for røde blodlegemer omfatter 15 -fortrinsvis et foretrukkent område for fiberoverfladearealet på fra ca. The filter assembly for red blood cells comprises 15 -fortrinsvis A preferred range for the fiber surface area of ​​from about 0,04 til ca. 0.04 to ca. 0,3 m3, fortrinsvis fra ca. 0.3 m 3, preferably from about 0,06 til ca. 0.06 to ca. 0,20 m2. 0.20 m 2. Et foretrukkent område for strømningsarealet for det porøse medium er fra ca. A preferred range for the flow area of ​​the porous medium is from about 3 til ca. 3 to ca. 8 cm2, og et mere foretrukkent område ligger fra ca. 8 cm2, and a more preferred range is from about 4 til ca. 4 to about 6 cm2. 6 cm2. Et 20 foretrukkent område for hulrumsrumfanget ligger fra ca. 20 A preferred range for the voids volume is from about 71 til ca. To about 71 83%, og et mere foretrukkent område fra ca.· 73 til ca. 83%, and a more preferred range of from about 73 to about · 80%. 80%. På grund af dets ringe størrelse udviser et foretrukkent organ i overensstemmelse med denne variation typisk et lavt "hold-up"-rumfang. Because of its small size, exhibit a preferred body in accordance with this variation typically low "hold-up" -rumfang. Når f.eks. When, for example. det biologiske fluidum, 25 der behandles, er PRP, tilbageholder organet i overensstemmelse med denne variation i det indre kun ca. the biological fluid being treated 25, the PRP, retaining means in accordance with this variation in the internal only about 0,5 til ca. 0.5 to ca. 1 cm3 PRP, hvilket repræsenterer mindre end et 0,5%'s tab af blodplader. 1 cm 3 of PRP, representing less than a 0.5% loss of platelets.

Med en anden variation af de omhandlede organer eller 30 sammensætninger ledes PRP afledt fra en enkelt enhed på ca. As another variation of these bodies or 30 compositions passed the PRP derived from a single unit of about

450 cm3 humant blod, typisk under et strømningsinterval på fra ca. 450 cm 3 of human blood, typically during a flow interval of about 10-40 minutter, gennem et filter indeholdende et porøst medium, fortrinsvis indeholdende podede fibre, med et overfladeareal i området fra ca. 10-40 minutes, through a filter comprising a porous medium, preferably comprising grafted fibers, with a surface area in the range of about 0,08 til ca. 0.08 to ca. 1,0 m2, og 35 mere fortrinsvis fra ca. 1.0 m 2, and 35 more preferably from about 0,1 til ca. 0.1 to ca. 0,7 m2, med et hulrumsrumfang i området fra ca. 0.7 m2 with a voids volume in the range from about 50% til ca. 50% to ca. 89%, fortrinsvis i----------—— - 89%, preferably in ------------ -

DK 175916 B1 I In DK 175916 B1

fra ca. from about 60 til ca. To about 60 85%. 85%. Filterelementet har fortrinsvis ret I The filter element is preferably of right I

cylindrisk form med forholdet mellem diameter og tykkelse I cylindrical shape with the ratio between the diameter and thickness in

fortrinsvis i området fra ca. preferably in the range from about 7:1 til ca. 7: 1 to about 40:1. 40: 1. Området for I The area of ​​I

fiberdiameteren foretrækkes at ligge fra ca. the fiber diameter is preferred to be from about 1,0 til ca. 1.0 to ca. 4 I 4 L

5 μτη, navnlig i området fra ca. 5 μτη, in particular in the range from about 2 til ca. 2 to ca. 3 μχη. 3 μχη. I relation I In relation I

til den tidligere variation foretages denne variation med I to the previous variation shall be carried out this variation of I

højere fiberoverfladeareal, højere gennemstrømningsareal I higher fiber surface area, higher flow area I

for porøst medium, mindre massefylde for porøst medium og I the porous medium of lower density porous medium and in

et forøget hulrumsvolumen. an increased void volume. I IN

10 Alle disse parametre kan varieres. 10 All of these parameters can be varied. Eksempelvis kan I For example, the I

diameteren af det porøse medium formindskes og tykkelsen I the diameter of the porous medium and the thickness is reduced in

forøges, idet man bibeholder det samme totale antal fibre, I increases as maintaining the same total number of fibers, In

eller fibrene kan have en større diameter, idet den totale I or the fibers may have a larger diameter, the total I

mængde fibre forøges, eller fibrene kan pakkes i modsætning I amount of fibers is increased, or the fibers can be packaged in opposition in

15 til for-formning til en cylindrisk skive. 15 to pre-forming into a cylindrical disc. Sådanne variationer I Such variations in

falder inden for opfindelsens rammer. fall within the scope of the invention. I IN

En anden variation kan omfatte et porøst medium, i I Another variation may comprise a porous medium, in the I

hvilket opstrøms-delen har en højere massefylde end ned- I which the upstream portion having a higher density than the reduced I

strøms-delen. Power moiety. Eksempelvis kan det porøse medium indeholde I For example, the porous medium contain at

20 et opstrømslag med højere massefylde til blokering af pas- I 20 upstream layer with a higher density for blocking the passport In

sagen af røde blodlegemer og et nedstrømslag med lavere I the case of red blood cells and a lower nedstrømslag In

massefylde til fjernelsen af leucocyter. density for the removal of leucocytes. I IN

Ifølge én udførelsesform for opfindelsen er fibrene I According to one embodiment of the invention, the fibers in the

overflademodificeret på samme måde som i de forudgående I surface modified in the same manner as in the previous I

25 versioner, men fiberoverfladearealelementet forøges, medens I 25 versions, but the fiber surface area element is increased while the I

massefylden samtidig formindskes noget. density while alleviating anything. På denne måde kom- I In this way com- In

bineres den automatiske blokering af strømning ved kontakt I combined the automatic blockage of flow on contact in

med røde blodlegemer med meget høj effektivitet af leucocyt- I with the red blood cells with very high efficiency of leukocyte In

fjernelse. removal. I IN

30 Et foretrukkent område for fiberoverfladeareal i I 30 A preferred range for the fiber surface area in the I

forbindelse med denne variation af opfindelsen ligger fra H the purpose of this variation of the invention is at H

ca. ca. 0,3 til ca. 0.3 to ca. 2,0 m2, og et mere foretrukkent område ligger H 2.0 m2, and a more preferred range is H

fra ca. from about 0,35 til ca. 0.35 to ca. 0,6 m2. 0.6 m 2. De øvre grænser for fiberover- I The upper limits of fiberover- In

fladeareal afspejler ønsket om at gennemføre filtreringen i I surface area reflects the desire to implement filtering in I

35 løbet af et forholdsvis kort tidsrum og kan forøges, såfremt I 35 within a relatively short period of time and may be increased if I

længere filtreringstidsrum kan accepteres. longer filtration time is acceptable. Et foretrukkent H A preferred H

DK 175916 B1 35 hulrumsrumfang for barrieresammensætningen for de røde blodlegemer ligger i området fra ca. DK 175916 B1 void volume 35 of the barrier composition of the red blood cells is in the range from about 71 til ca. To about 71 83%, fortrinsvis fra ca. 83%, preferably from about 75 til ca. To about 75 80%. 80%. Et foretrukkent strømningsareal ligger fra ca. A preferred flow area is from about 2,5 til ca. 2.5 to ca. 10 cm2, og et mere foretrukkent 5 areal ligger fra ca. 10 cm2, and a more preferred 5 surface area is from about 3 til ca. 3 to ca. 6 cm2. 6 cm2. Leucocyt-fjernelses-effektiviteter ud over ca. Leucocyte depletion efficiencies in excess of about 99,9%, der svarer til et gennemsnitligt resterende leucocytindhold pr. 99.9%, which corresponds to an average residual per leucocytindhold. enhed på mindre end ca. unit of less than about 0,05 x 1O6, kan opnås. 0.05 x 1O6, can be obtained.

Ved en foretrukken udførelsesform for opfindelsen 10 kan et porøst medium til anvendelse med et biologisk fluidum såsom et ovenstående lag, f .eks.. PRP, omfatte den type organ, der er beskrevet i US patentskrift nr. 4.880.548, hvortil der henvises. In a preferred embodiment of the invention 10 may be a porous medium for use with a biological fluid such as a supernatant layer, e .g .. PRP, include the type of body that is disclosed in U.S. Pat. No. 4,880,548, incorporated herein by reference. Ifølge en foretrukken udførelsesform for opfindelsen kan et porøst medium til anvendelse sammen med et 15 biologisk fluidum, f.eks. According to a preferred embodiment of the invention, a porous medium for use with a biological fluid 15, for example. et sedimentlag, f.eks. a sediment layer, for example. PRC, omfatte den type organ, der er beskrevet i US patentskrift nr. 4.925.572 og i US patentskrift nr. 4.923.620, hvortil der henvises. PRC, include the type of body that is disclosed in U.S. Pat. No. 4,925,572 and in U.S. Pat. No. 4,923,620, incorporated herein by reference.

Som ovenfor angivet kan sediment1åget, f.eks. As indicated above, sediment1åget, for example. PRC, 20 når det udpresses fra opsamlingsposen, behandles gennem et organ med et leucocytfjernelseselement til formindskelse af leucocytindholdet i sedimentlaget. PRC, 20 when it is expressed from the collection bag, is processed through a body of a leucocyte for decreasing the leucocyte content of the sediment layer. Ifølge opfindelsen omfatter det porøse medium til fjernelse af leucocyter fra den pakkede røde blodlegemebestanddel af et biologisk fluidum et 25 leucocytf jernelseselement eller porøst medium. According to the invention, the porous medium for depleting leucocytes from the packed red cell component of a biological fluid 25 a leucocytf EMOVING element or porous medium. Det foretrukne element fremstilles typisk under anvendelse af bestrålingspodede, smelteblæste fibre med en gennemsnitlig diameter på fra ca. The preferred element is typically made using radiation grafted melt blown fibers having an average diameter of from about 1 til ca. 1 to ca. 4 μτη, fortrinsvis fra ca. 4 μτη, preferably from about 2 til ca. 2 to ca. 3 μπκ Polybutylenterephthalat (PBT)-væv, der er et foretrukkent 30 materiale, kan varmkomprimeres til et hulrumsrumfang på ca. 3 μπκ polybutylene terephthalate (PBT) tissue, which is a preferred material 30, may be hot compressed to a voids volume of about

65 til ca. 65 to ca. 90%, fortrinsvis til ca. 90%, preferably to about 73 til ca. To about 73 88,5%. 88.5%.

Separationssammensætning eller -organ Separation composition or body

Den foreliggende opfindelse omhandler separation af 35 en eller flere bestanddele fra et biologisk fluidum. The current invention concerns separation of 35 one or more components from a biological fluid. Et biologisk fluidum, navnlig blod, kan udsættes for et separa- A biological fluid, particularly blood, may be subjected to a separation

DK 175916 B1 I In DK 175916 B1

tionsmedium, der er egnet til at lade mindst én bestanddel I tion medium which is suitable for allowing at least one component of

af det biologiske fluidum passere, navnlig plasma, igennem I of passing the biological fluid, particularly plasma, through on the

mediet, men ikke andre bestanddele af det biologiske fluidum, I the medium, but not other components of the biological fluid, In

navnlig blodplader og/eller røde blodlegemer. particularly platelets and / or red blood cells. Tilstopning I clogging In

5 af separationsmediet med disse andre bestanddele minimeres I 5 of the separation medium by these other components is minimized In

eller forhindres. or prevented. I IN

I den udførelsesform, der omfatter en separationssam- I In the embodiment comprising a separationssam- In

mensætning 14, fortrinsvis et separationsorgan uden centrifu- composition 14, preferably a centrifugal separation device without

gering, kan det ovenstående lag, f.eks. alloy, may be the supernatant layer, for example. PRP, ledes gennem H PRP is passed through H

10 et leucocytfjernelsesorgan og dernæst ledes gennem separa- I 10 is a leucocytfjernelsesorgan and then passed through the separation I

tionsorganet 14 uden centrifugering, hvor det kan behandles I tion means 14, without spinning, in which it can be processed in

og adskilles i bestanddele, der separat kan opsamles i en I and separated into components which can be separately collected in an I

beholder 15 og en beholder 16. I en foretrukken udførelses- H container 15 and a container 16. In a preferred performance H

form kan den ovenstående væske, hvis denne er PRP, adskilles I form, the supernatant, if the PRP is separated into

15 i plasma og blodpladekoncentrat, når PRP passerer gennem H 15 in plasma and platelet concentrate as the PRP passes through the H

separationsorganet uden centrifugering. separation device without centrifugation. I IN

Som vist i fig. As shown in FIG. 5 omfatter et foretrukkent separa- I 5 comprises a preferred separation I

tionsorgan et hus 210 med første og anden dele 210a, 210b H tion means a housing 210 having first and second portions 210a, 210b H

forbundet på enhver bekvem måde. connected in any convenient manner. Eksempelvis kan de første H For example, the first H

20 og anden husdele 210a, 210b være forbundet ved hjælp af et I 20 and second housing portions 210a, 210b be connected by means of an I

klæbemiddel, et opløsningsmiddel eller et eller flere forbin- I adhesive, a solvent, or one or more connection I

delsesorganer. partly sorrow ancestry. Hust 210 har også et indløb 211 og første og I Hust 210 also has an inlet 211 and first and In

anden udløb 212 og 213, således at der etableres en første second outlet 212 and 213, so as to establish a first

fluid strømningsbane 214 mellem indtaget 211 og det første I fluid flow path 214 between the inlet 211 and the first I

25 udtag 212, og en anden fluid strømningsbane 215 etableres I 25 outlet 212, and a second fluid flow path 215 is established in

mellem indtaget 11 og det andet udtag 13. Et separationsme- I between the intake 11 and the second outlet 13. In a separationsme-

dium 216 med første og anden overflader 216a, 216b er anbragt I medium 216 having first and second surfaces 216a, 216b are arranged in

inden i huset 210 mellem de første og anden husdele 210a, I within the housing 210 between the first and second housing portions 210a, In

210b. 210b. Endvidere er separationsmediet 216 anbragt parallelt H Further, the separation medium 216 arranged in parallel H

30 med den første fluid strømningsbane 214 og tværs over den H 30 with the first fluid flow path 214 and across the H

anden fluid strømningsbane 215. H second fluid flow path 215. The H

Udførelsesformer for den foreliggende opfindelse kan H Embodiments of the present invention, the H

være udformet på en række forskellige måder til sikring af I be designed in a variety of ways to ensure I

maksimal kontakt mellem det biologiske fluidum og den første I maximum contact between the biological fluid and the first in

35 overflade 216a af separationsmediet 216 og til formindskelse I 35 surface 216a of the separation medium 216 and to decrease in

eller eliminering af tilstopning på den første overflade I or eliminate clogging on the first surface in

DK 175916 B1 37 216a af separationsmediet. DK B1 175 916 37 216a of the separation medium. Eksempelvis kan separationsorganet omfatte et første fladt kammer, der vender mod den første overflade 216a af separationsmediet 216. Det første kammer kan omfatte et arrangement af ribber, der spreder strømningen 5 af biologisk fluidum over hele den første overflade 216a af separationsmediet 216. Alternativt kan det første kammer omfatte én eller flere kanaler, riller, ledninger, passager eller lignende, der have serpentinekonfiguration, parallel, kurvet eller en lang række andre konfigurationer. For example, the separating means comprise a first flat chamber, which faces the first surface 216a of the separation medium 216. The first chamber may include an arrangement of ribs which spread the flow 5 of biological fluid over the entire first surface 216a of the separation medium 216. Alternatively, the first chamber may comprise one or more channels, grooves, conduits, passages, or the like, which have serpentine, parallel, curved, or a variety of other configurations.

10 Fluidumstrømningskanalerne kan have enhver egnet ud formning og konstruktion. The fluid flow channels 10 may have any suitable construction and forming out. Eksempelvis kan kanalerne have et rektangulært, triangulært eller halvcirkulært tværsnit og en konstant dybde. For example, the channels may have a rectangular, triangular or semi-circular cross section and a constant depth. Kanalerne har fortrinsvis et rektangulært tværsnit og varierer i dybde, f.eks. The channels preferably have a rectangular cross section and vary in depth, for example. mellem indløbet 211 og 15 udløbet 212. between the inlet 211 and the outlet 15 212th

I den udførelsesform, der er vist i fig. In the embodiment shown in FIG. 6, 7 og 8, er indløbet 211 i huset 210 forbundet til serpentine-fluidumstrømningskanaler 220, 221 og 222, der vender mod den første overflade 216a af separationsmediet 216. Disse kanaler 220-20 222 adskiller den indkommende strømning af biologisk fluidum i særskilte strømningsbaner tangentielt til den første overflade 216a af separationsmediet 216. Strækkende sig langs den første overflade 216a kan serpentine-f luidumstrømningska-naler 220, 221 og 222 genkombineres ved det første udløb 25 212 fra huset 210. 6, 7 and 8, the inlet 211 of the housing 210 connected to the serpentine-fluidumstrømningskanaler 220, 221 and 222, facing the first surface 216a of the separation medium 216. These channels 220 to 20,222 separates the incoming flow of biological fluid into separate flow paths tangentially to the first surface 216a of the separation medium 216. Extending along the first surface 216a can be serpentine-f luidumstrømningska signals 220, 221 and 222 may be recombined at first outlet from the housing 25212 210th

Udførelsesformer for opfindelsen kan også udformes på en række måder til minimering af tilbagetryk tværs over separationsmediet 216 og til sikring af en tilstrækkeligt høj hastighed for strømningen til det andet udløb 212 til 30 hindring af forurening af overfladen 216a, idet "hold-up"-rumfanget minimeres. Embodiments of the invention can also be designed in a number of ways to minimize back pressure across the separation medium 216 and to ensure a sufficiently high velocity of flow to the second outlet 212 to 30 prevent contamination of the surface 216a, as "hold-up" -rumfanget minimized. Separationsorganet omfatter et andet fladt kammer, der vender mod den anden overflade 216b af separationsmediet 216. Ligesom det første kammer kan det andet kammer omfatte et arrangement af ribber eller kan 35 indeholde én eller flere kanaler, riller, ledninger, passager eller lignende, der kan have konfigurationer i form af ser- The separation means comprises a second flat chamber facing the second surface 216b of the separation medium 216. Like the first chamber, the second chamber include an arrangement of ribs or may 35 contain one or more channels, grooves, conduits, passages, or the like, which can be having configurations in the form of Ser

DK 175916 B1 I In DK 175916 B1

pentiner, parallelle eller kurvede eller en række andre I pentiner, parallel or curved, or a variety of other I

konfigurationer. configurations. I IN

Fluidumstrømningskanalerne kan have enhver egnet ud- I The fluid flow channels may have any suitable lending In

formning og konstruktion. forming and construction. Eksempelvis kan kanalerne have et I For example, the channels may have an I

5 rektangulært, halvcirkulært eller triangulært tværsnit og I 5 rectangular, semi-circular or triangular cross-section and

en konstant eller variabel dybde. a constant or variable depth. I den udførelsesform, der I In the embodiment, the I

er vist i fig. is shown in Fig. 9-11, vender flere serpentine-fluidumstrøm- I 9-11, several serpentine turns in fluidumstrøm-

ningskanaler 231, 232, 233, 234 og 235 mod den anden over- I ducts 231, 232, 233, 234 and 235 against the other top In

flade 216b af separationsmediet 216. Strækkende sig langs den I surface 216b of the separation medium 216. Extending along the I

10 anden overflade 216b kan serpentine-fluidumstrømningskanaler- I 10 second surface 216b may be serpentine in fluidumstrømningskanaler-

ne 231-235 genkombineres ved det andet udløb 213. H ne 231-235 recombined at the second outlet 213. The H

Ribber, vægge eller fremspring 241, 242 kan anvendes I Ribs, walls, or projections 241, 242 may be used in

til at definere kanalerne 220-222, 231, 232-235 af det første I to define the channels 220-222, 231, 232-235 of the first I

og andet kammer og/eller kan understøtte eller anbringe I and second chambers and / or may support or position the I

15 seperationsmediet 216 i huset 210. I en foretrukken udførel- I 15 separation medium 216 within the housing 210. In a preferred execution in

sesform for opfindelsen findes der flere vægge 242 i det andet kammer end i det første kammer til hindring af defor- mation af separationsmediet 216, forårsaget af trykdifferen- sesform of the invention, there are more walls 242 in the second chamber than in the first chamber to prevent deformation of the separation medium 216 caused by pressure differential

tialet gennem separationsmediet. potential is through the separation medium. I IN

20 Ved anvendelsen ledes et biologisk fluidum, f.eks. 20 By the application is passed a biological fluid, for example. I IN

helblod eller PRP, under tilstrækkeligt tryk ind i indløbet I whole blood or PRP, under sufficient pressure into the inlet I

211 af huset 210 fra enhver egnet kilde til det biologiske I 211 of the housing 210 from any suitable source of the biological In

fluidum. fluid. Eksempelvis kan det biologiske fluidum injiceres fra I For example, the biological fluid is injected from the I

en injektionssprøjte i indløbet 211, eller det kan tvinges I an injection syringe into the inlet 211 or it may be forced into

25 ind i indløbet 211 fra en fleksibel pose under anvendelse I 25 into the inlet 211 from a flexible bag using I

af tyngdekraftens påvirkning, en trykmanchet eller et udpres- I by the influence of gravity, a pressure cuff or a udpres- In

ningsorgan. member. Fra indløbet 211 træder det biologiske fluidum I From the inlet 211 enters the biological fluid in

ind i kanalerne 220-222 i det første kammer og passerer I into the channels 220-222 of the first chamber and passes

tangentielt eller parallelt til den første overflade 216a I tangentially or parallel to the first surface 216a in

30 af separationsmediet 216 på vej til det første udløb 212 I 30 of the separation medium 216 on the way to the first outlet 212

via den første fluidumstrømningsbane 214. Mindst én bestand- I via the first fluid flow path 214. At least one constituent in

del af det biologiske fluidum, f.eks. portion of the biological fluid, for example. plasma, passerer gennem I plasma, passes through the I

separationsmediet 216, træder ind i kanalerne 231-235 i det I separating medium 216, shall enter into the channels 231-235 in the In

andet kammer og ledes mod det andet udløb 213 via den anden H second chamber and is directed towards the second outlet 213 via the second H

35 fluidumstrømningsbane 215. Efterhånden som det biologiske I 35 fluid flow path 215. As the biological In

fluidum fortsætter langs den første strømningsbane 214 tan- I fluid continues along the first flow path 214 in tandem

DK 175916 B1 39 gentielt eller parallelt med den første overflade 216a af separationsmediet 216, krydser mere og mere plasma separationsmediet 216. Et plasmafattigt fluidum udtræder derefter fra huset 210 ved det første udløb 212 og udvindes i en beholder 5 217, medens plasma træder ud af huset 210 ved det andet udløb 213 og opsamles i en anden beholder 218. DK 175916 B1 39 gentielt or parallel to the first surface 216a of the separation medium 216, cross the more and more plasma separation medium 216. A plasma-poor fluid withdraws then from the housing 210 at the first outlet 212 and is recovered in a container 5217, while plasma exits the the housing 210 at the second outlet 213 and is collected in a second container 218th

Om end ethvert biologisk fluidum indeholdende plasma kan anvendes i forbindelse med den foreliggende opfindelse, er opfindelsen navnlig velegnet til anvendelse i forbindelse 10 med blod og blodprodukter, navnlig helblod eller PRP. While any biological fluid containing plasma may be used in the context of the present invention, the invention is particularly well suited for use in connection 10 with blood and blood products, especially whole blood or PRP. Ved at underkaste PRP behandling i overensstemmelse med den foreliggende opfindelse kan PC og blodplade-frit plasma opnås uden centrifugering af PRP og de dermed forbundne ulemper, der er diskuteret ovenfor. By subjecting PRP to treatment according to the present invention, PC and platelet-free plasma obtained without centrifugation of the PRP and the attendant disadvantages discussed above. Ligeledes kan der fås 15 blodpladefrit plasma fra helblod. Also, to give 15 platelet-free plasma from whole blood. Det biologiske fluidum kan tilføres i enhver egnet mængde, der er forenelig med kapaciteten af det samlede organ og ved hjælp af vilkårlige egnede midler, f.eks. The biological fluid may be supplied in any suitable quantity consistent with the capacity of the overall body and by means of any suitable means, for example. ved en batch-operation, f.eks. in a batch operation, for example. ved hjælp af en blodpose forbundet med et udpresningsorgan eller 20 en injektionssprøjte, eller ved en kontinuerlig operation som en del af f.eks. with the aid of a blood bag connected to an expressor or 20 an injection syringe, or in a continuous operation as part of, for example. et aferesesystem. an apheresis system. Eksempler på kilder til biologisk væske omfatter en injektionssprøjte 219 som vist i fig. Exemplary sources of biological fluid include a syringe 219 as shown in Fig. 5 eller et opsamlings- og behandlingssystem for biologisk fluidum som f.eks. 5, or a collection and processing system for the biological fluid, such as. beskrevet i US patentansøgning 25 nr. 07/609.654, der er indleveret den 6. november 1990, og hvortil der henvises. described in US patent application 25 no. 07 / 609,654, filed November 6, 1990, and incorporated herein by reference. En kilde til biologisk fluidum kan også omfatte et aferesesystem og/eller kan omfatte et system, i hvilket biologisk fluidum recirkuleres gennem systemet. A source of biological fluid may also include an apheresis system, and / or may comprise a system in which biological fluid is recirculated through the system.

Separationsmediet og huset kan være fremstillet af 30 et vilkårligt egnet materiale og med vilkårlig konfiguration, og separationsmediet kan være anbragt i det her omhandlede organ ifølge opfindelsen på enhver egnet måde, blot den biologiske fluidumstrøm tangentielt eller parallelt med separationsmediet opretholdes i en tilstrækkelig grad til at 35 undgå eller minimere væsentlig blodplade-adhæsion til separationsmembranen. The separation medium and housing may be made of 30 any suitable material and of any configuration and the separation medium may be arranged in the present inventive device according to the invention in any suitable manner, only the biological fluid flow tangential or parallel to the separation medium is maintained to a sufficient extent to 35 to avoid or minimize substantial platelet adhesion to the separation membrane. De hydrodynamiske strømningsforhold paral- The hydrodynamic flow conditions parallel

40 I 40

DK 175916 B1 I In DK 175916 B1

lelt til en overflade antages faktisk at være således be- I lelt to a surface believed actually to be such confirm In

skafne, at blodplader under strømning parallelt med over- I skafne that platelets during flow parallel to the upper I

fladen udvikler et spin, der bevirker, at de kan udvindes I surface develops a spin which causes that they can be recovered in

fra overfladen. from the surface. Medens det foretrukne organ har et indløb I While the preferred means having an inlet in

5 og to udløb, kan andre konfigurationer anvendes uden uønsket I 5 and two outlets, other configurations can be used without undesirable in

påvirkning af den korrekte funktion af organet. effect on the proper operation of the device. Eksempelvis I For example, in

kan der anvendes multiple indløb for et biologisk fluidum, I may be used multiple inlets for a biological fluid, in

blot det biologiske fluidum strømmer tangentielt tværs over I only the biological fluid flows tangentially across the I

overfladen af separationsmediet. the surface of the separation medium. Plasmaet kan fortrinsvis I The plasma may preferably I

10 opbevares i et område adskilt fra separationsmediet til I 10 is stored in a region separated from the separation medium to I

undgåelse af mulig reverseret strømning af plasmaet tilbage j I avoid possible reverse flow of the plasma back j I

tværs over separationsmediet til det plasmafattige fluidum. across the separation medium to the plasma-poor fluid. I IN

Fagmanden vil forstå, at blodplade-adhæsion kan re- I The skilled artisan will recognize that platelet adhesion may be re- In

guleres eller påvirkes ved manipulering af en vilkårlig af I guleres or affected by manipulating any of the I

15 et antal faktorer: hastighed af fluidumstrømningen, kon- I 15 a number of factors: velocity of the fluid flow, in con-

figuration af kanalen, dybde af kanalen, variation af kana- I configuration of the channel, depth of the channel, varying the kanamycin I

lens dybde, separationsmediets overfladekarakteristika, I Lens Depth, separation medium surface characteristics, In

mediets overfladeglathed og/eller den vinkel, under hvilken I surface smoothness of the medium and / or the angle at which the I

fluidumstrømmen krydser overfladen af separationsmediet, I the fluid flow crosses the face of the separation medium in

20 blandt andre faktorer. 20, among other factors. Eksempelvis er hastigheden af den I For example, the speed of the I

første fluidumstrømning fortrinsvis tilstrækkelig til fjer- I first fluid flow is preferably sufficient to feathers- In

nelse af blodplader fra overfladen af separationsmediet. formation of blood platelets from the surface of the separation medium. I IN

Uden at skulle begrænses dertil har det vist sig, at en I Without being limited thereto, it has been found that an I

hastighed på mere end ca. rate of greater than about 30 cm/sekund er passende. 30 cm / sec is appropriate. I IN

25 Hastigheden af fluidumstrømmen kan også påvirkes af I 25 The velocity of the fluid flow can also be influenced by I

rumfanget af det biologiske fluidum, ved variation af kanal- I the volume of the biological fluid, by varying the channel I

dybden, og ved hjælp af kanalbredden. depth, and by means of the channel width. Eksempelvis kan kanal- I For example, the channel I

dybden varieres fra ca. depth varied from about 6,35 til ca. 6.35 to ca. 0,025 mm som vist i I 0.025 mm as shown in the I

fig. FIG. 7. Fagmanden vil forstå, at en ønsket hastighed kan I 7. The skilled person will recognize that a desired velocity may be in

30 opnås ved manipulation af disse og andre elementer. 30 is achieved by manipulating these and other elements. Endvidere I In addition,

er det muligt, at blodplader ikke vedhænger så let til et I it is possible that platelets are not so easily adheres to an I

separationsmedium, der har en glat overflade, som til en I separation medium having a smooth surface, to which an I

membran, der har en mere ru overflade. membrane having a rougher surface. I IN

Ifølge opfindelsen omfatter separationsmediet et I According to the invention, the separation medium is an I

35 porøst medium, der er egnet til gennemledning af plasma. 35 porous medium suitable for passing plasma. I IN

Det her anvendte separationsmedium kan omfatte, men er ikke I As used herein the separation medium may include, but is not in

41 DK 175916 B1 begrænset til polymere fibre, herunder hule fibre, polymere fibermatrixer, polymere membraner og faste porøse medier. 41 DK 175916 B1 limited to polymeric fibers, including hollow fibers, polymeric fiber matrices, polymeric membranes, and solid porous media. Separationsmedier ifølge opfindelsen fjerner plasma fra en biologisk opløsning indeholdende blodplader, typisk helblod 5 eller PRP, uden fjernelse af proteinholdige blodbestanddele og uden at tillade en væsentlig.mængde blodplader at passere igennem. Separation media according to the invention removes plasma from a biological solution containing platelets, typically whole blood or PRP 5, without removing proteinaceous blood components and without allowing a væsentlig.mængde platelets to pass through.

Et separationsmedium ifølge opfindelsen udviser fortrinsvis en gennemsnitlig porestørrelse, der generelt eller iO iboende er mindre end den gennemsnitlige størrelse af blodplader, og blodplader klæber fortrinsvis ikke til overfladen af separationsmediet, hvorved poreblokering formindskes. A separation medium according to the invention preferably exhibits an average pore size which is generally iO intrinsic or is less than the average size of platelets, and platelets preferably not adhered to the surface of the separation medium, wherein the pore blocking is reduced. Separationsmediet bør også have eri lav affinitet til proteinholdige bestanddele i det biologiske fluidum, f.eks. The separation medium should also have ERI low affinity for proteinaceous components in the biological fluid, for example. PRP. PRP.

15 Dette forøger sandsynligheden for, at den blodpladefattige opløsning, f.eks. 15, this increases the likelihood that the platelet-poor solution, for example. blodpladefrit plasma, vil udvise en normal koncentration af proteinholdige koagulationsfaktorer, vækstfaktorer og andre påkrævede bestanddele. platelet-free plasma will exhibit a normal concentration of proteinaceous clotting factors, growth factors and the other required ingredients.

Til separation af ca. For separation of ca. én enhed af helblod kan et 20 typisk separationsorgan ifølge opfindelsen omfatte en effektiv porestørrelse mindre end blodplader i gennemsnit, typisk mindre end 4 mikrometer, fortrinsvis mindre end 2 mikrometer. one unit of whole blood, a typical separation device 20 according to the invention comprise an effective pore size smaller than platelets on the average, typically less than 4 micrometers, preferably less than 2 microns. Permeabiliteten og størrelsen af separationsorganet er fortrinsvis tilstrækkelig til produktion af ca. The permeability and size of the separation device is preferably sufficient to produce about 160 cm3 til 25 ca. 160 cm 3 to about 25 240 cm3 plasma ved rimelige tryk, f.eks. 240 cm 3 of plasma at reasonable pressures, for example. mindre end ca. less than about

1,4 kg/cm^, i løbet af et rimeligt tidsrum, f.eks. 1.4 kg / cm ^, over a reasonable period of time, for example. mindre end 1 time. less than 1 hour. Ifølge opfindelsen kan alle disse typiske parametre varieres til opnåelse af et ønsket resultat, dvs. According to the invention, all of these typical parameters varied to achieve a desired result, i.e., varieres fortrinsvis til minimering af blodpladetab og til 30 maksimering af blodpladefri plasmaproduktion. varied preferably to minimize platelet loss and 30 to maximize platelet-free plasma production.

I overensstemmelse med opfindelsen kan et separationsmedium fremstillet af fibre være kontinuerligt, indeholdende stabelfibre eller smelteblæste fibre. In accordance with the invention, a separation medium made of fibers be continuous, containing staple fibers, or meltblown fibers. Fibrene kan fremstilles ud fra ethvert materiale, der er foreneligt med et biologisk 35 fluidum indeholdende blodplader, f.eks. The fibers can be made from any material that is compatible with a biological fluid containing 35 platelets, for example. helblod eller PRP, og kan behandles på en række forskellige måder til at gøre whole blood or PRP, and may be treated in a variety of ways to make

DK 175916 B1 I In DK 175916 B1

mediet mere effektivt. media more effectively. Fibrene kan også være bundet, sam- I The fibers may also be bound, co-I

mensmeltet eller på anden måde fikseret til hverandre, eller I Fusion Bonded or otherwise fixed to each other, or In

de kan simpelthen være mekanisk sammensnoet. they may simply be mechanically entwined. Et separations- H A separation H

medium tildannet af en membran, således som dette udtryk I medium formed of a membrane, as that term I

5 her anvendes, refererer til ét eller flere porøse polymere I 5 is used here, refers to one or more porous polymers I

ark, f.eks. sheets, for example. et vævet eller uvævet væv af fibre, med eller I a woven or non-woven web of fibers, with or I

uden et fleksibelt porøst substrat, eller kan omfatte en I without a flexible porous substrate, or may comprise an I

membran tildannet ud fra en polymeropløsning i et opløsnings- I membrane formed from a polymer solution in a solvent in

middel ved fældning af en polymer, når polymeropløsningen I agent by precipitation of a polymer when the polymer solution in the

10 bringes i kontakt med et opløsningsmiddel, i hvilket den I 10 is contacted with a solvent in which the I

polymere ikke er opløselig. polymer is not soluble. Det porøse, polymere ark vil I The porous, polymeric sheet will

typisk have en i det væsentlige ensartet, kontinuerlig ma- I typically have a substantially uniform, continuous maleic In

trix-struktur indeholdende en myriade af små, i det væsent- I matrix structure containing a myriad of small, essentially in the In

lige indbyrdes forbundne porer. straight interconnecting pores. I IN

15 Separationsmediet ifølge opfindelsen kan f.eks. 15 The separation medium according to the invention may, for example. frem- I In manufacturing

stilles ud fra en vilkårlig syntetisk polymer, der kan danne I be prepared from any synthetic polymer that can form I

fibre eller en membran. fibers or a membrane. Om end det ikke er nødvendigt for Although not necessary

det omhandlede apparat eller den omhandlede metode, er den I the apparatus or the subject method, it is in

polymere ifølge en foretrukken udførelsesform i stand til I polymers of a preferred embodiment in a position in

20 at tjene som et substrat til podning med ethylenisk umættede I 20 to serve as a substrate for grafting with ethylenically unsaturated In

monomere materialer. monomeric materials. Den polymere bør fortrinsvis være i I The polymer should preferably be in the In

stand til at reagere med mindst én ethylenisk umættet monomer I capable of reacting with at least one ethylenically unsaturated monomer I

under indflydelse af ioniserende stråling eller andre akti- I under the influence of ionizing radiation or other The shares In

verende midler, uden at matrixen påvirkes i uønsket retning. -activating agents without the matrix being adversely affected. I IN

25 Egnede polymere til anvendelse som substratet omfatter, men 25 Suitable polymers for use as the substrate include, but

er ikke begrænset til polyolefiner, polyestere, polyamider, I are not limited to polyolefins, polyesters, polyamides, In

polysulfoner, polyarylenoxider og -sulfider, og polymere og I polysulfones, polyarylene oxides and sulfides, and polymers and I

copolymere fremstillet ud fra halogenerede olefiner og umæt- I copolymers made from halogenated olefins and unsaturated In

tede nitriler. through the nitriles. Foretrukne polymere er polyolefiner, poly- I Preferred polymers are polyolefins, poly I

30 estere og polyamider, f.eks. 30 esters, and polyamides, for example. polybutylenterephthalat (PBT) I polybutylene terephthalate (PBT) in

og nylon. and nylon. I en foretrukken udførelsesform kan en polymer- I In a preferred embodiment, a polymer-I

membran fremstilles ud fra en fluoreret polymer såsom poly- I membrane is prepared from a fluorinated polymer such as poly I

vinylidendifluorid (PVDF) . vinylidene difluoride (PVDF). De mest foretrukne separationsme- I The most preferred separationsme- In

dier er en mikroporøs polyamidmembran eller en polycarbonat- I values ​​are a microporous polyamide membrane or polycarbonate in

35 membran. 35 membrane. I IN

Overfladeegenskaberne for en fiber eller membran kan I The surface properties of a fiber or membrane can

DK 175916 B1 43 påvirkes som ovenfor bemærket for et porøst medium. DK 175916 B1 43 are affected as noted above for a porous medium. Et eksempel på bestrålings-podningsteknik gør anvendelse af mindst én af en række monomere, der hver indeholder en ethylen-eller acrylisk del og en anden gruppe, der kan vælges fra 5 hydrofile grupper, f.eks. An exemplary radiation grafting technique employs at least one of a number of monomers each comprising an ethylene or acrylic moiety and a second group which can be selected from 5 hydrophilic groups, for example. -COOH eller -OH, eller hydrofobe grupper, f.eks. -COOH or -OH, or hydrophobic groups, for example. en methylgruppe eller mættede kæder såsom -CH2CH2CH3. a methyl group or saturated chains such as -CH2CH2CH3. Podning af fiberen eller membranoverfladen kan også udføres med forbindelser indeholdende en ethylenisk umættet gruppe, f.eks. Grafting of the fiber or membrane surface may also be accomplished with compounds containing an ethylenically unsaturated group, for example. en acrylisk molekyldel, kombineret 10 med en hydroxylgruppe, f.eks. an acrylic moiety combined with a hydroxyl group 10, for example. hydroxyethylmethacrylat (HEMA). hydroxyethyl methacrylate (HEMA). Anvendelse af HEMA som den monomere bidrager til en meget høj CWST-værdi. Use of HEMA as the monomer contributes to a very high CWST. Analoge med lignende egenskaber kan også anvendes til at modificere fibrenes overfladeegenskaber. Analogs with similar properties can also be used to modify the surface characteristics of fibers.

I overensstemmelse med en udførelsesform for opfin-15 delsen kan separationsmediets overflade modificeres, typisk ved bestrålingspodning, til opnåelse af ønskede ydeevnekarakteristika, hvorved blodplader koncentreres med et minimidm af medieblokering, og hvorved den resulterende plasmaopløsning indeholder i det væsentlige alle dens native protein-20 holdige bestanddele. In accordance with an embodiment of the inventors 15 period, the separation medium is surface modified, typically by bestrålingspodning, to achieve desired performance characteristics, whereby platelets are concentrated with a minimidm of medium blocking, and whereby the resulting plasma solution contains essentially all of its native protein-20 containing components. Eksempler på membraner med en lav affinitet for proteinholdige stoffer er beskrevet i US patent-skrifterne nr. 4.886.836, nr. 4.906.374, nr. 4.964.989 og nr. 4.968.533, hvortil der henvises. Exemplary membranes having a low affinity for proteinaceous substances are disclosed in U.S. Patent Nos. 4,886,836, no. 4,906,374, no. 4,964,989 and no. 4,968,533, incorporated herein by reference.

Egnede membraner i overensstemmelse med en udførel-25 sesform for opfindelsen kan være mikroporøse membraner og kan fremstilles ved en opløsningsstøbningsmetode. Suitable membranes in accordance with an embodiment, 25 sesform of the invention may be microporous membranes and may be produced by a solution casting method.

Som nævnt ovenfor bevirker etablering af en tangentiel strømning af det biologiske fluidum, der behandles, parallelt med eller tangentielt til overfladen af separationsmediet 30 minimering af blodpladeopsamling i eller passage gennem separationsmediet. As mentioned above, causes the creation of a tangential flow of the biological fluid being processed parallel with or tangential to the surface of the separation medium 30 minimize platelet collection in or passage through the separation medium. Ifølge opfindelsen kan den tangentielle strømning fremkaldes ved enhver mekanisk konfiguration af den strømningsbane, der inducerer en høj lokal fluidumhastighed ved den umiddelbare membranoverflade. According to the invention the tangential flow can be induced by any mechanical configuration of the flow path which induces a high local fluid velocity at the immediate membrane surface. Det tryk, der 35 driver det biologiske fluidum tværs over separationsmediet, kan opnås på enhver egnet måde, f.eks. The pressure 35 drives the biological fluid across the separation medium may be achieved in any suitable manner, for example. ved tyngdekraftens by gravity

DK 175916 B1 I In DK 175916 B1

hjælp eller ved hjælp af et udpresningsorgan. or by means of an expressor. I IN

Den tangentielle strømning af det biologiske fluidum I The tangential flow of the biological fluid in

kan rettes tangentielt eller parallelt til overfladen af I can be directed tangentially or parallel to the surface of the In

separationsmediet på enhver egnet måde, fortrinsvis under I the separation medium in any suitable manner, preferably under I

5 anvendelse af en væsentlig del af separationsmediets over- I 5 the use of a substantial part of the separation medium In the upper

flade under opretholdelse af tilstrækkelig strømning til I surface, while maintaining sufficient flow to I

sikring af, at blodpladerne ikke tilstopper eller blokerer I ensure that the platelets do not clog or block the I

porerne i separationsmediet. the pores of the separation medium. Strømmen af det biologiske I The flow of the biological In

fluidum er fortrinsvis rettet tangentielt eller parallelt med I fluid is preferably directed tangentially or parallel to I

10 overfladen af separationsmediet ved anvendelse af mindst én I 10 the surface of the separation medium by using at least one I

serpentine-fluidumstrømningskanal, der er udformet til at I serpentine fluid flow channel which is designed to In

maksimere udnyttelse af separationsmediet, sikre en til- I maximize utilization of the separation medium, ensure to-In

strækkelig total arealkontakt mellem det biologiske fluidum sufficiently total area contact between the biological fluid

og separationsmediet samt opretholdelse af en tilstrækkelig I and the separation medium and the maintenance of an adequate In

15 strømning af biologisk fluidum til minimering eller hindring 15 the flow of biological fluid to minimize or prevent

af blodplade-adhæsion til separationsmediet. of platelet adhesion to the separation medium. Fortrinsvis I preferably in the

anvendes der flere, f.eks. If several, for example. tre eller flere fluidumstrømnings- I three or more fluid flow in

kanaler til fiksering af separationsmediet på plads og til I channels for fixation of the separation medium in place and to I

hindring af sætning af membranen på grund af det påførte I preventing the addition of the membrane due to the applied I

20 tryk. 20 pressure. Fluidumstrømningskanalerne kan have enhver egnet ud- I The fluid flow channels may have any suitable lending In

formning og konstruktion og er fortrinsvis variable med I shaping and construction and preferably are variable with I

hensyn til dybde, f.eks. respect to depth, for example. dybde til opnåelse af optimalt I depth to obtain optimal I

tryk og fluidumstrømning tværs over overfladen af separa- I pressure and fluid flow across the surface of the separator in

tionsmediet. medium. Fluidumstrømningskanaler kan også anvendes på I Fluidumstrømningskanaler may also be used on the I

25 siden af separationsmediet modsat den tangentielle strømning H 25 the side of the separation medium opposite to the tangential flow H

af biologisk fluidum til regulering af strømningshastigheden H of the biological fluid for regulation of the flow rate H

og tryktab for et blodpladefattigt fluidum, f.eks. and pressure drop of a platelet-poor fluid, for example. plasma. plasma. H H

Det her omhandlede organ kan ligeledes være del af H The present inventive device may also be part of H

et aferesesystem. an apheresis system. Det biologiske fluidum, der skal behandles, H The biological fluid to be processed, H

30 den blodpladerige opløsning og/eller den blodpladefattige I 30 the platelet-rich solution, and / or the platelet-poor

opløsning kan håndteres enten batchvis eller på kontinuerlig H solution can be handled either batchwise or in a continuous H

måde. manner. Størrelsen, naturen og konfigurationen af det her I The size, nature and configuration of this I

omhandlede organ kan reguleres til variation af kapaciteten H referred to body can be regulated to vary the capacity H

af organet til tilpasning til dets tilsigtede omgivelser. of the means for alignment with its intended environment. H H

35 I 35

DK 175916 B1 45 DK 175916 B1 45

Gasindløb/gasudtaq Gas inlet / gasudtaq

Under visse omstændigheder kan det være ønskeligt at maksimere udvindingen af et biologisk fluidum tilbageholdt eller indesluttet i forskellige elementer af behandlings-5 systemet for det biologiske fluidum. Under certain circumstances it may be desirable to maximize the recovery of a biological fluid retained or entrapped in various elements of the processing system 5 of the biological fluid. Eksempelvis vil det biologiske fluidum under typiske betingelser under anvendelse af et typisk organ drænes gennem systemet, indtil strømningen standses, idet noget af fluidet efterlades i systemet. For example, the biological fluid under typical conditions, using a typical means is drained through the system until flow is stopped, since some of the fluid is left in the system. I én udførelsesform for opfindelsen kan dey tilbageholdte fluidum 10 udvindes ved anvendelse af mindst ét gasindløb og/eller mindst ét gasudtag. In one embodiment of the invention, dey retained fluid 10 is recovered by using at least one gas inlet and / or at least one gas outlet means. Et eksempel på konfigurationen af denne udførelsesform er vist i fig. An example of the configuration of this embodiment is shown in Fig. 3. Third

Gasudløbet er et porøst medium, der tillader gas, der kan være til stede i et behandlingssystem for et biolo-15 gisk fluidum, når det biologiske fluidum behandles i systemet, at træde ud af systemet. The gas outlet is a porous medium which allows gas that may be present in a processing system for a liquid c-logical fluid 15 when the biological fluid processed by the system to step out of the system. Gasindløbet er et porøst medium, der indfører gas i et behandlingssystem for et biologisk fluidum. The gas inlet is a porous medium, which introduces gas in a processing system for a biological fluid.

Som her benyttet refererer udtrykket gas til ethvert 20 gasformigt fluidt medium, f.eks. As used herein, the term gas 20 to any gaseous fluid, for example. luft, steriliseret luft, oxygen, carbondioxid og lignende. air, sterilized air, oxygen, carbon dioxide, and the like. Det er hensigten, at opfindelsen ikke skal begrænses til den anvendte type gas. It is intended that the invention not be limited to the type of gas.

Gasindløbet og gasudløbet vælges således, at systemets sterilitet ikke kompromitteres. The gas inlet and gas outlet are chosen such that sterility of the system is not compromised. Gasindløbet og gasudløbet 25 er særlig egnet til anvendelse i lukkede systemer, eller de kan anvendes senere, f.eks. The gas inlet and the gas outlet 25 is particularly suitable for use in closed systems, or may be used later, for example. indenfor ca. within ca. 24 timer fra åbningen af et system. 24 hours from the opening of a system.

Gasindløbet og gasudløbet omfatter hver mindst ét porøst medium udformet til at tillade gas at passere igennem 30 det. The gas inlet and the gas outlet each comprise at least one porous medium designed to allow gas to pass through it 30. En række forskellige materialer kan anvendes, forudsat at de pågældende egenskaber for det bestemte porøse medium opnås. A variety of materials can be used, provided that the properties of the particular porous medium are obtained. Disse omfatter den nødvendige styrke til håndtering af de differentielle tryk, der forekommer ved anvendelsen, og evnen til at tilvejebringe den ønskede filtreringskapa-35 citet under tilvejebringelse af den ønskede permeabilitet, uden anvendelse af ekscessivt tryk. These include the necessary strength to handle the differential pressure that occurs in the application, and the ability to provide the desired filtreringskapa-35 capacity while providing the desired permeability without the application of pressure ekscessivt. I et sterilt system bør ii In a sterile system should II

I DK 175916 B1 I In DK 175916 B1 In

I 46 1 1 in 46

I det porøse medium også fortrinsvis have en porestørrelse på I In the porous medium also preferably have a pore size of I

I ca. In ca. 0,2 mikrometer eller mindre til hindring af bakteriepas- I 0.2 micron or less to prevent bakteriepas- In

I sage. In sage. I IN

I Gasindløbet og gasudløbet kan indeholde et porøst I In the gas inlet and gas outlet may contain a porous I

I 5 medium, f.eks. In 5 medium, for example. et porøst, fibrøst medium, såsom et dybfilter, I a porous fibrous medium, such as a dybfilter, In

I eller en porøs membran eller et porøst ark. I or a porous membrane or a porous sheet. Porøse medier I Porous Media In

I bestående af flere lag kan anvendes, f.eks. In consisting of more layers can be used, for example. en flerlagsmi- I In one flerlagsmi-

I kroporøs membran, hvor ét lag er liquofobt og det andet er I The microporous membrane in which one layer being liquophobic and the other is I

I liquofilt. In liquophilic. I IN

I 10 Foretrukne udgangsmaterialer er syntetiske polymere, I In 10 Preferred starting materials are synthetic polymers, In

I herunder polyamider, polyestere, polyolefiner, navnlig poly- I In including polyamides, polyesters, polyolefins, in particular poly I

I propylen og polymethylpenten, perfluorerede polyolefiner, I In propylene and polymethylpentene, perfluorinated polyolefins, In

I f.eks. In example. polytetrafluorethylen, polysulfoner, polyvinyliden- I polytetrafluoroethylene, polysulfones, polyvinylidene In

I difluorid, polyacrylonitril og lignende, og kompatible bian- I In difluoride, polyacrylonitrile and the like, and compatible bian- In

I 15 dinger af polymere. In 15 mixtures of polymers. Den mest foretrukne polymer er polyvinyl- I The most preferred polymer is polyvinyl In

I idendifluorid. In idendifluorid. Indenfor klassen af polyamider omfatter de I Within the class of polyamides include those described in

I foretrukne polymerer polyhexamethylenadipamid, poly-e-capro- I In the preferred polymers include polyhexamethylene adipamide, poly-e-capro- In

I lactam, polymethylensebacamid, poly-7-aminoheptanoamid, I In lactam, polymethylene, poly-7-aminoheptanoamid, In

I polytetramethylenadipamid {nylon 46) eller polyhexamethyl- I In polytetramethylene adipamide {nylon 46) or polyhexamethyl- In

I 20 enazeleamid, idet polyhexamethylenadipamid (nylon 66) navnlig I In enazeleamid 20, with polyhexamethylene adipamide (nylon 66), particularly in

I foretrækkes. I is preferred. Særligt foretrukne er hudfri, i det væsentlige I Particularly preferred are hudfri, substantially in

I alkohol-uopløselige, hydrofile polyamidmembraner såsom de, I In the alcohol-insoluble, hydrophilic polyamide membranes, such as those in

I der er beskrevet i US patentskrift nr. 4.340.479. In those described in U.S. Pat. No. 4,340,479. I IN

I Andre udgangsmaterialer kan også anvendes til at I In Other starting materials may also be used to I

I 25 fremstille de porøse medier, herunder cellulosederivater, 25 In producing the porous media, including cellulose derivatives,

I f.eks. In example. celluloseacetat, cellulosepropionat, celluloseacetat- I cellulose acetate, cellulose propionate, cellulose acetate In

I propionat, celluloseacetat-butyrat og cellulosebutyrat. In propionate, cellulose acetate butyrate and cellulose butyrate. I IN

I Ikke-harpiksholdige materiale, f.eks. In Non-resinous materials, for example. glasfibre, kan også I glass fibers, can also be in

I anvendes. I apply. I IN

I 30 Hastigheden af luftstrøm gennem gasudløbet eller I In 30 The rate of air flow through the gas outlet or I

I gasindløbet kan tilpasses det specifikke biologiske fluidum I In the gas inlet can be adapted to the specific biological fluid

eller de biologiske fluida, der har interesse. or the biological fluids of interest. Hastigheden I The speed In

I af luftstrømmen varierer direkte med arealet af det porøse I In the air flow varies directly with the area of ​​the porous I

I medium og det påsatte tryk. In the medium and the applied pressure. Anmindeligvis er arealet af det I Anmindeligvis is the area of ​​the In

I 35 porøse medium udformet til at bevirke, at behandlingssystemet I In the porous medium 35 configured to cause the processing system In

I for det biologiske fluidum primes i et påkrævet tidsrum under I In the biological fluid is primed in a required time under I

DK 175916 B1 47 anvendelsesbetingelserne. DK 175916 B1 47 the conditions of use. Eksempelvis er det ved medicinske anvendelser ønskeligt at være i stand til at prime et intravenøst sæt i fra ca. For example, in medical applications it is desirable to be able to prime an intravenous set in from about 30 til ca. To about 30 60 sekunder. 60 seconds. Ved sådanne anvendelser såvel som ved andre medicinske anvendelser er 5 det typiske porøse medium en membran, der kan have form af en skive med en diameter fra ca. In such applications as well as in other medical applications is 5, the typical porous medium is a membrane which may take the form of a disk with a diameter of about 1 mm til ca. 1 mm to about 100 mm, fortrinsvis fra ca. 100 mm, preferably from about 2 mm til ca. 2 mm to ca. 80 mm, og navnlig fra ca. 80 mm, and most preferably from about 3 mm til ca. 3 mm to ca. 25 mm. 25 mm.

I overensstemmelse med opfindelsen kan behandlings-10 sytemet være udstyret med et gasindløb for at tillade indføring af gas i systemet, og/eller med et gasudløb til at tillade gasser i de forskellige elementer i systemet at blive adskilt fra det biologiske fluidum, der skal behandles. According to the invention, the processing 10 sytemet be equipped with a gas inlet to permit the introduction of gas into the system, and / or with a gas outlet to permit gases in the various elements of the system to be separated from the biological fluid to be treated . Gasindløbet og gasudløbet kan anvendes sammen i forbindelse 15 med mindst ét samlet, porøst medium eller en beholder i systemet, eller de kan anvendes særskilt. The gas inlet and the gas outlet may be used together in connection 15 with at least one single, porous medium, or container in the system, or may be used separately.

Til dette formål kan et gasindløb eller gasudløb være inkluderet i ethvert af de forskellige elementer af behandlingssystemet for det biologiske fluidum. For this purpose, a gas inlet or gas outlet may be included in any of the various elements of the processing system for the biological fluid. Som illustra- 2 0 tion kan nævnes, at et gasindløb eller gasudløb kan være inkluderet i mindst én af de ledninger, der forbinder de forskellige beholdere, i en væg af beholderne, der modtager det behandlede biologiske fluidum, eller i en åbning på eller i én af disse beholdere. As illustrative 2 0 tion can be mentioned that a gas inlet or gas outlet may be included in at least one of the wires that connect the different containers, in a wall of the containers that receive the processed biological fluid, or in an opening on or in the one of those containers. Gasindløbet eller gasudløbet kan 25 også være inkluderet på eller i en kombination af de ovennævnte elementer. The gas inlet or the gas outlet 25 may also be included on or in a combination of the above elements. En sammensætning eller et porøst medium kan også inkludere ét eller flere gasindløb eller gasudløb som ovenfor beskrevet. A composition or a porous medium may also include one or more gas inlet or gas outlet as described above. Generelt foretrækkes det imidlertid at inkludere et gasindløb eller gasudløb i de ledninger, 3 0 der forbinder beholderne, eller i det funktionelle medicinske organ. In general, it is preferred to include a gas inlet or gas outlet in the conduits 3 0 connecting the containers or in the functional medical body. Omfattet af opfindelsens omfang er anvendelsen af | Included within the scope of the invention is the use of | mere end ét gasindløb eller gasudløb i enhver ledning, modtagende beholder, sammensætning eller porøst medium. more than one gas inlet or gas outlet in any conduit, receiving container, composition or porous medium.

Det vil være åbenbart for en fagmand på området, at 35 anbringelsen af et gasindløb eller et gasudløb kan optimeres til opnåelse af et ønsket resultat. It will be apparent to one skilled in the art that the arrangement 35 of a gas inlet or a gas outlet may be optimized to obtain a desired result. Eksempelvis kan det For example, the

I DK 175916 B1 I In DK 175916 B1 In

I 48 I In 48

I være ønskeligt at lokalisere gasindløbet opstrøms fra et I In may be desirable to locate the gas inlet upstream from an I

I porøst medium og i eller så tæt til den første beholder som I In the porous medium and in or as close to the first container as In

I praktisk muligt til maksimering af udvindingen af biologisk I In practicable to maximize the recovery of biological In

I væske. In fluid. Det kan også være ønskeligt at lokalisere gasudløbet I It may also be desirable to locate the gas outlet In

I 5 nedstrøms for det porøse medium og så tæt til den modtagende I In 5 downstream of the porous medium and as close to the receiving I

I beholder som muligt til maksimering af det rumfang gas, der I In the container as possible to maximize the volume of gas that I

I fjernes fra systemet. In is removed from the system. I IN

I En sådan placering af gasindløbet eller gasudløbet I In such a location of the gas inlet or gas outlet in

I er navnlig ønskelig, når der kun forefindes ét gasindløb I In is particularly desirable when only be provided in one gas inlet

10 eller gasudløb i systemet. 10 or the gas outlet in the system. I IN

I Udvinding fra de forskellige elementer af behandlings- I The extraction from the various elements of the treatment I

I systemet for det biologiske fluidum kan maksimeres. In the system of the biological fluid can be maximized. Eksenpel- I Eksenpel- In

I vis underkastes helblod et behandlingstrin, der resulterer I In some whole blood is subjected to a processing step, which results in

I i særskilte PRP- og PRC-lag. In in separate PRP and PRC layers. Dernæst udpresses de særskilte I Then squeezed out the separate I

I 15 fraktioner af blodbestanddele til deres respektive modtage- I The 15 fractions of blood components to their respective receiving I

I beholdere gennem passende ledninger og porøse medier, såfremt I In containers through the appropriate conduits and porous media, if I

I sådanne forefindes. In any. Blodprodukt, der er blevet indesluttet I Blood product that has been trapped in

I i disse elementer under behandlingen, kan udvindes enten I In in these elements during processing may be recovered either in

I ved at lede skyllegas gennem ledningerne og porøse medier, I In by directing purge gas through the conduits and porous media, I

I 20 eller ved tilvejebringelse af i det mindste et partielt I In 20, or by providing at least a partial In

I vakuum i systemet til udtrækning af det tilbageholdte blod- I In the vacuum in the system for extracting the retained blood In

I produkt og for at tillade det at løbe ind i den pågældende I In the product and allow it to run into the In

I modtagebeholder eller sammensætning. In the receiving vessel or composition. I IN

I Skylle- eller rensegassen kan hidrøre fra en vilkårlig I In the flushing or the purging gas can be derived from any I

I 25 af et antal kilder. In 25 of a number of sources. Eksempelvis kan behandlingssystemet for H For example, the processing system for the H

I det biologiske fluidum være udstyret med en opbevaringsbehol- I In the biological fluid to be equipped with a opbevaringsbehol- In

I der til opbevaring af skyllegassen, og skyllegassen kan være I In the storage of the purge gas, and the purge gas may be in

I den gas, der fjernes fra systemet under behandlingsfunktio- I In the gas which is removed from the system during behandlingsfunktio- In

I nen, eller skyllegassen kan injiceres aseptisk i systemet I In the moon, or the purge gas may be injected aseptically into the system in

I 30 fra en ydre kilde, f .eks. In 30 from an external source, e .g. gennem en injektionssprøjte. through a syringe. Eksem- H By way of H

I pelvis kan det være ønskeligt at anvende steril skyllegas, I In the pelvis, it may be desirable to use sterile purge gas, In

I der er blevet steriliseret i en særskilt beholder adskilt I In that have been sterilized in a separate container apart in

I fra behandlingssystemet for det biologiske fluidum. In the processing system for the biological fluid. I IN

I En klemme, et lukke eller lignende kan være anbragt I In A clamp, closure, or the like may be arranged in

I 35 på eller i enhver af eller alle ledningerne til lettelse af H In 35 on or in any or all of the conduits to facilitate H

I en ønsket funktion, dvs. In a desired feature, i.e., etablering af en ønsket strømnings- H establishing a desired flow H

DK 175916 B1 49 bane for biologisk væske eller gas. DK 175916 B1 49 path for biological fluid or gas. Når der f.eks. When, for example. behandles et biologisk fluidum, f.eks. treated a biological fluid, for example. PRP, gennem et system, således som det er illustreret i fig. PRP, through a system such as illustrated in FIG. 3, kan det under fjernelsen af gasser fra ledningerne og leucocytfjernelsessammensætnin-5 gen være ønskeligt at afspærre ledningen umiddelbart under gasudløbet 54. Når det er ønskeligt at anvende gasindløbet 53 til at maksimere udvindingen af et biologisk fluidum, frigøres klemmen under gasudløbet 54, og en klemme i ledningen stødende op til gasindløbet 53 åbnes. 3, it can be during the removal of gases from the conduits and leucocytfjernelsessammensætnin-5 gene may be desirable to close off the conduit immediately below gas outlet 54. When it is desirable to use the gas inlet 53 to maximize the recovery of a biological fluid, the clamp is released during the gas outlet 54, and a clamp in the conduit adjacent to the gas inlet 53 is opened. Som eksemplificeret i 10 fig. As exemplified in Figure 10. 3 kan andre gasindløb og gasudløb, f.eks. 3, other gas inlets and gas outlets, for example. 51 og 52, bringes til at fungere på lignende måde. 51 and 52, be made to function in a similar manner.

Under fortsat henvisning til fig. With continued reference to FIG. 3 vil en søjle af biologisk fluidum, f.eks. 3, a column of biological fluid, for example. PRP, når den strømmer fra den første beholder 11 gennem ledningen og leucocytf j emel sessam-15 mensætningen 13 mod satellitposen 41, drive gassen i disse elementer mod gasudløbet 54. PRP as it flows from the first container 11 through the conduit and leucocytf j Emel sessam-15 composition 13 toward the satellite bag 41, drive the gas in those elements towards the gas outlet 54th

Gasudløbet kan omfatte et forgreningselement med tre ben. The gas outlet may comprise a branching element with three legs. Ét ben kan omfatte et liquofobt porøst medium, der fortrinsvis har en porestørrelse på ikke mere end 0,2 μ. One leg may include a liquophobic porous medium which preferably has a pore size of not more than 0.2 μ.

20 Ved forgreningselementet bevæger gas, der er foran søjlen af biologisk fluidum, sig ind i det ene ben af forgreningselementet. 20 at the branching element moving gas that is in front of the column of biological fluid moves into one leg of the branching element. Eftersom gassen passerer gennem det liquofobe porøse medium, men det biologiske fluidum ikke gør dette, adskilles gassen fra PRP og hindres i at træde ind i satel-25 litposen 15. Since the gas passes through the liquophobic porous medium, but the biological fluid does not, the gas is separated from the PRP and is prevented from entering the satellites 25-litposen 15th

De gasser, der adskilles ved gasudløbet 54, kan af-luftes fra systemet, eller de kan opsamles i en gasbeholder (ikke vist på tegningen) og returneres til systemet som en skyllegas til lettelse af udvindingen af biologisk fluidum, 30 der bliver indesluttet i de forskellige bestanddele af systemet . The gases separated by the gas outlet 54, may be de-aerated from the system, or they may be collected in a gas container (not shown) and returned to the system as a purge gas to facilitate the recovery of biological fluid, 30 which is enclosed in the various components of the system.

Efter at systemet er primet, og gasudløbet er inak-tiveret, åbnes klemmen stødende op til beholderne eller sammensætningen for at tillade beholderne at blive fyldt 35 med behandlet biologisk fluidum. After the system is primed and the gas outlet is inactivated-inactive, opens the clamp adjacent to the containers or the composition to allow the containers 35 to be filled with the treated biological fluid. Dette fortsætter, indtil opsamlingsposen 11 kollapser. This continues until the collection bag 11 collapses. Til udvinding af det særdeles For the production of the highly

50 I 50L

DK 175916 B1 I In DK 175916 B1

værdifulde biologiske fluidum, der er indeholdt i systemet, I valuable biological fluid contained in the system, In

kan luft fra omgivelserne eller en steril gas føres ind i can be ambient air or a sterile gas is fed into the

systemet gennem gasindløb 51 eller 53. Såfremt gasindløb 51 I the system through gas inlet 51 or 53. If gas inlet 51

eller 53 er manuelle indløb, åbnes et lukke, eller en klemme I or 53 are manual inlet, opens a closure, a clamp or In

5 frigøres. 5 is released. Hvis gasindløbene 51 eller 53 er automatiske, vil I If the gas inlets 51 or 53 is automatic, you will

trykforskellen mellem gasindløbet og beholderne bevirke, at I the pressure difference between the gas inlet and the containers cause the I

luften eller gassen strømmer gennem ledningerne, gennem de I the air or gas flow through the lines, through the I

porøse medier og mod de respektive beholdere. porous media, and towards the respective containers. Ved fremgangs- I By the procedure in

måden udvindes tilbageholdt biologisk fluidum, der er inde- I the mode is recovered retained biological fluid that is contained in

10 sluttet i disse elementer under behandlingen, fra disse kom- I 10 connected to these elements during the treatment of these com- In

ponenter og opsamles i beholderne. components and are collected in the containers. Det skal bemærkes, at I It should be noted that In

renseluft eller -gas fortrinsvis skilles fra det biologiske I purge air or gas is preferably separated from the biological In

fluidum ved gasudløbene 52 eller 54, således at kun lidt, om I fluid at the gas outlets 52 or 54 such that little, if I

nogen, rensegas vil blive modtaget af beholderne. any, purge gas will be received by the containers. Dette kan I This can

15 foretages ved at påsætte klemmer på ledningen nedstrøms fra I 15 is made by attaching terminals of the conduit downstream from the I

gasudløbet 52 eller 54. I en anden udførelsesform for op- I gas outlet 52 or 54. In another embodiment of the up I

findelsen kan renseluft eller -gas skilles fra systemet I The availability may purge air or gas is separated from the system in

gennem et gasudløb anbragt i selve posen. through a gas outlet located in the bag itself.

20 Konsol eller støtte I 20 A bracket I

I en anden udførelsesform er der tale om en konsol I In another embodiment, the case of a console In

eller støtte, der sikrer en filtersammensætning omfattende I or support that ensures a filter composition comprising In

et porøst medium eller én eller flere komponenter af en I a porous medium or one or more components of an I

sammensætning på plads under centrifugering, således at den I composition in place during centrifugation so that the I

25 eller de ikke beskadiges af de spændinger, der frembringes I 25, or they are not damaged by the tension that is generated in the

under centrifugering. during centrifugation. I IN

Blodopsamlings- og -behandlingsorganet 10, med én I Blood collection and -behandlingsorganet 10, with an I

eller flere satellitposer forbundet eller tilknyttet via en I or more satellite bags attached or connected via an I

ledning, kan anvendes integralt til fraskillelse af bestand- I conducting, may be used integrally to separate constituents in

30 dele fra helblod. 30 parts of whole blood. Denne udførelsesform kan bedre forstås I This embodiment may be better understood in

ved henvisning til den eksempelvise konfiguration, der er I by referring to the exemplary configuration, that is in

vist i fig. shown in Fig. 4. Under centrifugeringstrinet, ved hvilket I 4. During the centrifugation step at which I

røde blodlegemer koncentreres ved bunden af opsamlingsposen, I red cells concentrated at the bottom of the receiving bag, In

kan der frembringes kræfter på op til ca. one can generate forces of up to about 5000 gange tyngde- I 5000 times gravity in

35 kraften (5000 G) eller mere. 35 force (5000 G) or more. Opsamlingsposen er derfor for- I The collection bag is in front

trinsvis fleksibel, således som de øvrige poser er det, I preferably flexible so that the other bags is what you

DK 175916 B1 51 hvilket tillader dem at falde ned på bunden og mod væggene af en centrifugekurv 120, således at poserne selv kun underkastes små eller ingen spændinger. DK 175916 B1 51 allowing them to fall down on the bottom and against the walls of a centrifuge bucket 120, so that the bags themselves undergo only small or no tension.

I modsætning til fleksibiliteten og bøjeligheden af 5 poserne og rørene er det porøse medium typisk indeholdt i et stift plasthus (idet kombinationen heraf betegnes en filtersammensætning). In contrast to the flexibility and pliability of the bags and the tubes 5, the porous medium is typically contained in a rigid plastic housing (the combination of which is termed a filter assembly). PRC-huset er typisk af større dimensioner end PRP-huset og er derfor udsat for en forøget sandsynlighed for at lide eller forårsage beskradigelse under 10 centrifugering. The PRC housing is typically of larger dimensions than the PRP housing, and is therefore subject to an increased probability of suffering or causing beskradigelse 10 during centrifugation. Eksempelvis kan en typisk PRC-filtersammensætning veje ca. For example, a typical PRC filter assembly weighing about 20 g, men dens effektive vægt kan være 5000 gange større, eller ca. 20 g, but its effective weight may be 5000 times greater, or about 100 kg, under centrifugerings-betingelser ved 5000 G. I konventionelle centrifugeringssystemer er det derfor vanskeligt at undgå knusning af plast-15 huset. 100 kg under centrifugation conditions of 5000 G. In conventional centrifugation systems it is therefore difficult to avoid the crushing of the plastic housing 15. Selv omhyggelig placering af PRC-filtersammensætningen i centrifugekurven vil sandsynligvis resultere i beskadigelse af plastrøret eller poserne. Even careful placement of the PRC filter assembly in the centrifuge bucket is likely to result in damage to the plastic tubing or bags. Endvidere er det uønsket at forøge størrelsen af centrifugekurven til at rumme filtersammensætningen i kurven under centrifugeringen, eftersom 20 dette ikke blot ville kræve anvendelse af en større og mere kostbar centrifuge, men også ville kræve fornyet træning og oplæring af de tusinder af blodbehandlingsteknikere til på kyndig vis at samle blodposesættene i en ny type centrifugekurv. Furthermore, it is undesirable to increase the size of the centrifuge bucket to accommodate the filter assembly in the basket during spinning, as 20, this would not only require the use of larger and more costly centrifuge, but also would require re-training, and training of the thousands of blood processing technicians to the knowledgeable some collecting blood bag sets into a new type of centrifuge basket.

25 Det er således ønskeligt, at et forbedret blodopsam lings- og -behandlingssystem eller -sæt skal kunne anvendes i forbindelse med eksisterende centrifugekurve. 25, it is desirable that an improved blood collection and processing system Guidance or kit could be used in conjunction with existing centrifuge buckets. I overensstemmelse med opfindelsen udføres dette fortrinsvis ved at anbringe PRC-filtersammensætningen borte fra den største G-30 kraft; According to the invention, this is realized preferably by arranging the PRC filter assembly away from the greatest force G-30; dette er fortrinsvis udenfor eller delvis udenfor den konventionelt anvendte centrifugekurv på den måde, der er vist i fig. This is preferably outside or partly outside of the conventionally used centrifuge bucket, in the manner shown in FIG. 4. 4th

I fig. In Fig. 4 er kurven 120 en centrifugekurv således, som en sådan anvendes i almindelig blodbankpraksis. 4, the curve 120 a centrifuge basket in such a way that one is used in normal blood bank practice. Disse 35 kurve er typisk konstrueret med tunge vægge af stål med høj styrke, der omslutter et åbent rum 121, i hvilket blodposen, These baskets 35 are typically constructed with heavy walls of high strength steel which enclose open space 121 into which the blood bag,

52 I 52

DK 175916 B1 I In DK 175916 B1

dens satellitposer og de tilsluttede rør kan anbringes. its satellite bags, and the connected pipe can be placed. Støt- I In aid

ten 122, der anvendes til at holde en filtersammensætning, I ten 122 which is used to hold a filter assembly, In

kan fremstilles af ethvert materiale med høj styrke, for- I can be made of any material with high strength, the front I

trinsvis metal eller en metallegering. preferably metal or a metal alloy. Titan eller rustfrit I Titanium or stainless In

5 stål foretrækkes navnlig på grund af deres styrke og den I 5 steel is particularly preferred because of their robustness and I

lethed, med hvilken sanitære betingelser kan opretholdes. ease with which sanitary conditions can be maintained. I IN

Den nedre den 123 af støtten 122 er udformet til kooperativt I The lower 123 of the bracket 122 is configured to cooperatively In

at passe i hulheden 121, fortrinsvis ved en dybde på fra I to fit in the cavity 121, preferably at a depth of from I

ca. ca. 0,5 til ca. 0.5 to ca. 1 cm. 1 cm. Fjederclips eller andre organer kan I Spring clips or other means may be in

10 anvendes til at anbringe og/eller fastholde støtten 122 i I 10 is used to position and / or retain bracket 122 in the I

kurven 120. Rillen eller fordybningen 124, der er anbragt i I curve 120. The groove or recess 124 which is disposed in the I

den øvre del af støtten 122, er fortrinsvis udformet til I the upper portion of bracket 122, is preferably configured to I

kooperativt at acceptere udgangsåbningen 125 af filtersam- I cooperatively accept the outlet port 125 of filtersam- In

mensætningen 114 og tillade bunddelen af filtersammensætnin- I composition 114 and allowing the bottom portion of filtersammensætnin- In

15 gen 114 at hvile på de plane øvre overflader af støtten 122 I 15 gene 114 to rest on the flat upper surfaces of bracket 122 in

stødende op til rillen 124. Den centrale del 126 af rillen I adjacent to the groove 124. The central portion 126 of the groove in the

eller fordybningen 124 kan være dimensioneret således, at I or the recess 124 may be sized such that I

åbningen 125 i filtersammensætningen 114 passer ind i mindst I the opening 125 of the filter assembly 114 fits into at least I

én del af rillen eller fordybningen 124 med en friktionspas- I one portion of the groove or recess 124 with a friktionspas- In

20 ning. 20 up. Enderne af fordybningen eller rillen 124 er fortrinsvis I The ends of the recess or groove 124 is preferably in the

reduceret til en bredde således, at det fleksible rør 112 I reduced to a width such that the flexible tube 112

forbundet til indløbet og udløbet af filtersammensætningen I connected to the inlet and outlet of the filter assembly in

114 fastholdes kraftigt, hvilket bidrager til at stabilisere I 114 is retained strongly, which helps to stabilize for

filtersammensætningen 114, når den anbringes på støtten I filter assembly 114 when placed on the support I

25 122. De uunderstøttede dele af det fleksible rør 112 falder I 25 122. The unsupported portions of the flexible tube 112 falls into

dernæst ind i kurven i forbindelse med resten af blodopsam- I then into the basket in relation to the rest of the blodopsam- In

lingssættet indeholdt deri. processing the set contained therein. Det foretrækkes, at støtten 122 I It is preferred that the bracket 122 in

fastholder filtersammensætningen 114 således, at planen for I maintains filter assembly 114 so that the I

det porøse medium er i det væsentlige vinkelret på den G- I the porous medium is substantially perpendicular to the G I

30 kraft, der frembringes under operation af centrifugen. 30 force generated during operation of the centrifuge. Støt- I In aid

te- og filtersammensætningen bør også være anbragt på eller I tea filter assembly should also be arranged on or in the

i centrifugekurven uden at interferere med den normale frit- I in the centrifuge bucket without interfering with the normal free-I

svingende virkning af kurven 120 i centrifugen under rota- I swinging action of the bucket 120 in the centrifuge during rotation In

tion. tion. I IN

35 Eftersom PRP-filteret typisk er forholdsvis lille og I 35 Because the PRP filter is typically relatively small and I

meget let, kan det anbringes inden i kurven med poserne og I very light, it can be placed within the basket with the bags and I

DK 175916 B1 53 røret. DK 175916 B1 53 pipe. I en anden udførelsesform kan rillen eller fordybningen 124 imidlertid være udformet til at holde mere end én filtersammensætning, f .eks. In another embodiment, the groove or the recess 124 may be designed to hold more than one filter assembly, e .g. både en PRC- og en PRP-filtersam-mensætning. both a PRC and a PRP filtersam-composition.

5 Ifølge en anden udførelsesform kan der anvendes en større støtte til at holde en første filtersammensætning, og en anden støtte, der holder en anden filtersammensætning, kan anbringes på toppen af den første støtte og f iltersanmen-sætning. 5 According to another embodiment, the use of a greater support to hold a first filter assembly, and a second support holding a second filter assembly may be placed on top of the first support and f iltersanmen statement. En fagmand vil være klar over de forskellige ud-10 formninger, konfigurationer og/eller organer, der kan anvendes til at opnå disse funktioner. One skilled in the art will recognize the various out-10 moldings, configurations and / or bodies can be used to achieve these functions.

Anbringelsen og den måde, på hvilken det porøse medium, navnlig PRC-mediet, monteres på centrifugekurven under centrifugeringsoperationen, er beskrevet i det følgende. The arrangement and the manner in which the porous medium, particularly the PRC medium, is mounted on the centrifuge bucket during the centrifugation operation is described below.

15 Forsøg med et antal testfilterhuse, der er udformet til at passe i centrifugekurven, har på overbevisende måde vist, at perforering af rørledninger ved huset er en hyppigt forekommende foreteelse under centrifugering. 15 Tests on a number of test filter housings designed to fit within the centrifuge bucket, has convincingly demonstrated that perforation of the pipelines by the housing is a frequent occurrence during centrifugation. Det er også særdeles vanskeligt at udforme et hus, der pålideligt kan modstå 20 påvirkningerne uden at blive ødelagt. It is also extremely difficult to design a house that can reliably withstand 20 impacts without being damaged. Endvidere er de eksisterende centrifugekurve udformet til at bære konventionelle blodopsamlingssæt, der ikke omfatter nogen filterelementer. Further, the existing centrifuge buckets designed to carry conventional blood collection, which includes no filter elements. Indpasning af det yderligere materiale bestående af en PRC-filtersammensætning i en konventionel kurv var således 25 særdeles vanskeligt. Integration of the additional material consisting of a PRC filter assembly in a conventional basket was thus 25 extremely difficult. Disse meget alvorlige problemer er blevet elimineret ved anbringelse af PRC-filtersammensætnin-gen på en støtte uden for kurven. These very serious problems have been eliminated by placing the PRC-filtersammensætnin gene on a support outside of the curve. Dette tilvejebringer passende understøtning for filtersammensætningen ved kooperativt arrangement af flangedelen 127 af støtten 122 (fig. 4) til 30 at rumme konturerne af centrifugekurven. This provides adequate support for the filter assembly by cooperatively arrangement of the flange portion 127 of bracket 122 (Fig. 4) to 30 to accommodate the contours of the centrifuge bucket. Endvidere er støtten 122 fortrinsvis anbragt over toppen af kurven, en position, der er meget tættere på centret for rotation i centrifugen, ! Furthermore, the bracket 122 is preferably positioned over the top of the curve, a position which is much closer to the center of rotation in the centrifuge,! således at den kraft, for hvilken filtersammensætningen udsættes, er ca. so that the force with which the filter assembly is subjected is about 40% til ca. 40% to ca. 60% af kraften ved bunden af 35 kurven 120. Desuden fastholder de snævre åbninger ved hver ende af støtten rørforbindelserne fast og tillader rørene 60% of the force at the bottom 35 of the basket 120. In addition, maintains the narrow openings at each end of the pipe connections fixed support and allows the tubes

DK 175916 B1 I In DK 175916 B1

at gå tilbage i skålen. to go back into the bowl. På overraskende måde tåler de suspen- H Surprisingly tolerate the suspension H

derede dele af rørene centrifugeringsoperationen særdeles H went off portions of the tubes spinning operation very H

godt. well.

Et system ifølge den foreliggende opfindelse kan H A system according to the present invention, H

5 anvendes i forbindelse med andre sammensætninger eller porøse H 5 is used in conjunction with other compositions or porous H

medier, herunder filtrerings- og/eller adskillelsesorganer, H media, including filtration and / or separation means, H

f.eks. eg. et organ til fjernelse af leucocyter fra en blodpla- a means for depleting leucocytes from a platelet

deholdig opløsning eller et blodpladeholdigt koncentrat. deholdig solution or a platelet concentrate. H H

Eksempler på sådanne organer er beskrevet i US patentskrift H Examples of such means are described in U.S. Pat H

10 nr. 4.880.548 og nr. 4.925.572. 10 no. 4,880,548 and no. 4,925,572. I IN

Huse kan fremstilles ud fra et vilkårligt egnet uigen- I Houses can be prepared from any suitable irrevocably In

nemtrængeligt materiale, herunder et uigennemtrængeligt H permeable material, including an impervious H

termoplastisk materiale. thermoplastic material. Eksempelvis kan huset fortrinsvis H For example, the housing may preferably H

fremstilles ved injektionsstøbning ud fra en transparent prepared by injection molding from a transparent

15 eller gennemskinnelig polymer, f.eks. 15 or translucent polymer, for example. en acryl-, polystyren- H an acrylic, polystyrene H

eller polycarbonatharpiks. or polycarbonate resin. Ikke blot er et sådant hus let H Not only is such a housing easily H

og økonomisk at fremstille, men det tillader også iagttagelse H and economical to manufacture, but it also allows observation H

af passagen af væsken gennem huset. of the passage of the fluid through the housing. H H

Det hus, i hvilket det porøse medium indesluttes H The housing in which the porous medium is enclosed H

20 eller fastgøres, er udformet til at give bekvem anvendelse, H 20 or attached, is designed to provide convenient use, H

hurtig priming og effektivt luftspillerum. rapid priming, and efficient air clearance. H H

Om end huset kan udformes i en række forskellige kon- H Although the housing can be designed in a variety of con- H

figurationer, indeholder huset af et porøst medium som her H figurations, includes the housing of a porous medium as here H

omhandlet fortrinsvis et hus såsom angivet i US patentskrif- H preferably provided for a housing such as disclosed in U.S. Patents H

25 terne nr. 4.880.548, nr. 4.923.620 og nr. 4.925.572, der I 25 States no. 4,880,548, no. 4,923,620 and no. 4,925,572, which

generelt svarer til konfigurationen af huset 114 i fig. generally corresponding to the configuration of the housing 114 of Fig. 4. H 4. H

Et antal yderligere beholdere kan være i forbindelse I A number of additional containers may be in the compound I

med behandlingssystemet for det biologiske fluidum og kan H with the treatment of the biological fluid and may be H

anvendes til at definere forskellige strømningsbaner. is used to define different flow paths. Eksem- H By way of H

30 pelvis kan en yderligere satellitpose indeholdende fysiolo- H 30 pelvis, an additional satellite bag containing physiological H

gisk opløsning anbringes i forbindelse med behandlingssy- H cally solution is placed in connection with the treatment services H

stemet for det biologiske fluidum opstrøms for leucocytfjer- I system for the biological fluid upstream of leucocytfjer- In

nelsesorganet, f.eks. formation means, for example. gennem gasindløbet, og opløsningen H through the gas inlet and the solution H

kan ledes gennem leucocytfjernelsesorganet således, at det H can be passed through the leucocyte depletion assembly so that the H

35 biologiske fluidum, der tilbageholdes i organet, kan opsam- H 35 biological fluid that was held up in the assembly can collecting H

les. les.

DK 175916 B1 55 På tilsvarende måde kan en satellitpose indeholdende fysiologisk opløsning anbringes i forbindelse med behandlingssystemet til det biologiske fluidum nedstrøms i forhold til leucocytfjernelsesorganet, f.eks. DK 175916 B1 55 Similarly, a satellite bag containing physiological solution may be placed in connection with the treatment system for the biological fluid downstream of the leucocyte depletion assembly, for example. gennem gasudløbet, og 5 opløsningen kan ledes gennem leucocytfjernelsesorganet således, at det biologiske fluidum, der tilbageholdes i organet, senere kan opsamles. through the gas outlet, and 5, the solution can be passed through the leucocyte depletion assembly so that the biological fluid that was held up in the assembly can be later collected.

Det vil forstås, at når det biologiske fluidum fra opsamlingsposen 11 trykkes ud mod beholderne, kan noget af 10 det biologiske fluidum indesluttes i ledningerne og/eller de porøse medier. It will be appreciated that when the biological fluid from the collection bag 11 is pressed out towards the containers, some of the biological fluid 10 trapped in the conduits and / or the porous media. Eksempelvis tilbageholdes der typisk fra 8 til 35 cm^ i systemet, men så lidt som fra 2 til så meget som 150 cm^ eller mere kan tilbageholdes i nogle typer systemer. For example, being held there typically 8-35 cm ^ in the system, but as little as 2 to as much as 150 cc or more may be retained in some types of systems.

15 I én udførelsesform (ikke vist på tegningen), kan luft eller gas opbevares i mindst én gasbeholder. 15 In one embodiment (not shown in the drawings), the air or gas is stored in at least one gas container. Ved åbning af ventil- eller klemorganer i ledningerne kan gas tilføres gennem dem til rensning eller skylning af ledningerne og sammensætningerne, hvorved man letter udvindingen af biolo-20 gi sk fluidum, der kan være blevet indesluttet vinder behandling . Upon opening of valve or clamp means in the conduits, gas can be supplied through them for cleaning or flushing of the lines and compositions, thereby facilitating the extraction of liquid c-20 g in SK fluid that may have become entrapped eventually treatment.

Fortrinsvis føres skylleluften eller -gassen til ledningerne ved et punkt, der er så tæt som rimeligt muligt til beholderen 11 til maksimering af rumfanget af det ud-25 vundne biologiske fluidum. Preferably said scavenging air or gas to the conduits at a point that is as close as reasonably possible to container 11 to maximize the volume of the out-25 obtained biological fluid. Luft- eller gasbeholderen er fortrinsvis fleksibel, således at gassen deri kan føres til systemet blot ved hjælp af simpel kompression. Air or gas container is preferably flexible so that gas therein may be fed to the system merely by simple compression. Beholderne for det biologiske fluidum og luft- eller gasbeholderne kan være sammensat af det samme materiale. The containers of the biological fluid and the air or gas containers may be composed of the same material.

30 Priming, således som dette udtryk anvendes her, re fererer til fugtning eller priming af de indre overflader af et organ eller en sammensætning inden den faktiske anvendelse, hvilket tillader, at en særskilt sammensætning injiceres i systemet. 30 Priming, as that term is used herein, re fererer to wetting or priming the inner surfaces of an organ, or a composition before the actual use, which allows a separate composition is injected into the system. En ventil eller klemme åbnes til at 35 tillade væske at strømme gennem sammensætningen. A valve or clamp is opened to allow the liquid 35 to flow through the composition. Dernæst, med passagen af væske gennem sammensætningen, udstødes gas Then, with the passage of liquid through the composition, are ejected gas

DK 175916 B1 I In DK 175916 B1

56 I 56

nedstrøms i forhold til væsken gennem gasudløbet, indtil I downstream of the liquid through the gas outlet until I

væsken når et forgreningselement, på hvilket punkt klemmen lukkes. fluid reaches a branching element, at which point the clamp is closed. Når klemmen er i en lukket stilling, kan forbindel- sesstykket nedstrøms fra gasudløbet åbnes eller gøres klar When the clip is in a closed position, the connecting piece downstream from the gas outlet opening or to prepare the

5 til anvendelse uden væske i sammensætningen dryppende gennem H 5 for use without fluid in the composition dripping through the H

forbindelsesstykket. connector. I IN

Den biologiske fluidumopsamlings- og -behandlingssam- I The biological fluidumopsamlings- and -behandlingssam- In

mensætning bør være i stand til at modstå kraftig sterilise- ring og centrifugering, typisk bestående af bestrålingsste- composition should be able to withstand vigorous sterilization and centrifugation, typically consisting of bestrålingsste-

10 rilisering (ved ca. 2,5 megarad) og/eller autoklavering I 10 sterilization (at about 2.5 megarads), and / or autoclaving for

(ved fra ca. 110 til ca. 120°C i fra ca. 15 til 60 minutter) I (At from about 110 to about 120 ° C for from about 15 to 60 minutes) In

og/eller centrifugering (typisk ved ca. 2500 til 3500 Gi I and / or centrifugation (typically at about 2500-3500 Gi I

fra ca. from about 5 til 15 minutter. 5 to 15 minutes. Afhængigt af den biologiske flui- I Depending on the biological fluid in

dumbestanddel, som ønskes udvundet maksimalt, kan centrifu- I dumbestanddel desired to be extracted from a maximum, the centrifugal In

15 geringen imidlertid foregå ved ca. 15, however, miter take place at about 5000 G i fra ca. 5000 G for about 10 til I 10 to I

20 minutter). 20 minutes). I IN

Ved en fremgangsmåde til opsamling og behandling af H In a method for the collection and treatment of H

blod opsamler man helblod i en beholder, centrifugerer hel- I blood comprising collecting whole blood in a container, centrifuging the whole I

blodet og leder det ovenstående lag af det centrifugerede H the blood and passing the supernatant layer of the centrifuged H

20 blod gennem et første porøst medium, hvilket første porøse I 20 blood through a first porous medium, the first porous I

medium indeholder mindst ét leucocytfjernelsesmedium, ét I medium containing at least one leucocyte depletion medium, one in

barrieremedium for røde blodlegemer og et kombineret leuco- I barrier medium for red blood cells and a combined leuco In

cytfjernelsesmedium og barrieremedium for røde blodlegemer, I cytfjernelsesmedium and barrier medium for red blood cells, In

hvorpå sedimentlaget af det centrifugerede blod ledes gennem I passing the sediment layer of the centrifuged blood is passed through the I

25 et andet porøst medium, hvilket andet porøse medium indehol- I 25 is a second porous medium, the second porous medium contain In

der et leucocytfjernelsesmedium. having a leucocyte depletion medium. I IN

Ved en fremgangsmåde til behandling af et biologisk I In a method for the treatment of a biological In

fluidum leder man et biologisk fluidum fra en første beholder I fluid conductor to a biological fluid from a first vessel in

til et første porøst medium indeholdende et barrieremedium I to a first porous medium comprising a barrier medium I

30 for røde blodlegemer, idet det biologiske fluidum ledes i en I 30 for red blood cells, since the biological fluid is passed into an I

første strømningsbane, og et biologisk fluidum ledes fra en H first flow path, and a biological fluid is directed from an H

første beholder til et andet porøst medium indeholdende et I first container to a second porous medium comprising an I

leucocytfjernelsesmedium, idet det biologiske fluidum ledes I leucocyte depletion medium, wherein the biological fluid is passed in

i en anden strømningsbane. in a second flow path. I IN

35 I almindelighed behandles donor-helblod så hurtigt I 35 In general, donated whole blood is treated as soon I

som praktisk muligt til mere effektivt at reducere eller I as practically possible to more effectively reduce or I

DK 175916 B1 57 eliminere forureningsfaktorer, herunder, men ikke blot leu-cocyter og mikroaggregater. DK 175 916 B1 57 eliminating pollution factors, including, but not only leu cocyter and microaggregates.

Leucucytfjernelse er tidligere typisk blevet udført under transfusion ved sengekanten, men i forbindelse med 5 den foreliggende opfindelse udføres leucucytfjernelse under den indledende behandling af helblodet, hvilket i praksis i USA i almindelighed foretages indenfor 8 timer fra aftapningen fra donoren. Leucucytfjernelse have previously typically been performed during transfusion at bedside, but in the context of the 5 present invention is carried leucucytfjernelse during the initial processing of the whole blood, which in practice in the United States generally be performed within 8 hours from draining from the donor. Efter at de røde blodlegemer er blevet sedimenteret ved centrifugering, udpresses den ovenstående 10 PRP fra blodopsamlingsposen i en første satellitpose gnenem et eller flere porøse medier, der formindsker mængden af leucocyter og/eller blokerer røde blodlegemer, og PRC, der forbliver i blodopsamlingsposen, ledes derpå gennem et porøst medium, der fjerner leucocyter i en anden satellitpose. After the red cells have been sedimented by centrifuging, squeezed out the above 10 PRP from the blood collection bag into a first satellite bag gnenem one or more porous media which diminish the amount of leucocytes and / or block red cells, and the PRC remaining in the blood collection bag, is passed then passed through a porous medium which removes leucocytes into a second satellite bag.

15 I almindelighed, jf. tegningens figurer, modtages | 15 In general, see. The drawing figures, receiving, | det biologiske fluidum, f.eks. the biological fluid, for example. donorens helblod, direkte i opsamlingsposen 11. Opsamlingsposen 11, med eller uden de øvrige elementer i systemet, kan dernæst centrifugeres til adskillelse af det biologiske fluidum i et ovenstående lag 20 31 og et sedimentlag 32. Efter centrifugering, såfremt der anvendes helblod, er det ovenstående lag primært PRP, og sedimentlaget er primært PRC. the donor's whole blood, directly into the collection bag 11. The collection bag 11, with or without the other elements of the system, may then be centrifuged to separate the biological fluid into a supernatant layer 20 31 and a sediment layer 32. After centrifugation, if used with whole blood, it is supernatant layer is primarily PRP, and the sediment layer is primarily PRC. Det biologiske fluidum kan udpresses fra opsamlingsposen som særskilte ovenstående og sedimentlag. The biological fluid may be expressed from the collection bag as separate above and sediment layers. Der kan forefindes en klemme eller lignende 25 mellem opsamlingsposen 11 og det fleksible rør 25, eller inden i røret, til hindring af strømningen af det ovenstående lag i at træde ind i den forkerte ledning. There may be provided a clip 25 or the like between the collection bag 11 and the flexible tube 25, or inside the tube, to prevent the flow of the supernatant layer from entering the wrong conduit.

Bevægelse af det biologiske fluidum gennem systemet foretages ved opretholdelse af et trykdifferentiale mellem 30 opsamlingsposen og bestemmelsesstedet for det biologiske fluidum, f.eks. Movement of the biological fluid through the system is effected by maintaining a pressure differential between the collection bag 30 and the destination of the biological fluid, for example. en beholder såsom en satellitpose eller en nål på enden af en ledning. a container such as a satellite bag or a needle on the end of a conduit. Systemet ifølge opfindelsen er egnet til anvendelse sammen med konventionelle organer til etablering af trykdifferentialet, f.eks. The system according to the invention is suitable for use with conventional means for establishing the pressure differential, for example. en ekspressor. one expressor.

35 Eksempler på organer til etablering af dette trykdifferentiale er organer til tilvejebringelse af tyngdekraftpåvirk- 35 Exemplary means of establishing this pressure differential is means for providing tyngdekraftpåvirk-

DK 175916 B1 I In DK 175916 B1

58 I 58

ning, påsætning af tryk på opsamlingsposen, f.eks. Ning, applying pressure to the collection bag, for example. manuelt I In manually

eller ved hjælp af en trykmanchet, eller ved anbringelse af I or by means of a pressure cuff, or by placing in

den anden beholder, f.eks. the second container, for example. satellitpose, i et kammer, f.eks. satellite bag in a chamber, for example.

et vakuumkammer, der etablerer et trykdifferentiale mellem I a vacuum chamber which establishes a pressure differential between the I

5 opsamlingsposen og den anden beholder. 5 the collecting bag and the second container. Der kan også anvendes I There can also be used in

ekspressorer, der frembringer i det væsentlige samme tryk I expressors which generate substantially equal pressure in

over hele opsamlingsposen. over the entire collection bag. I IN

Når det biologiske fluidum passerer fra en pose til I When the biological fluid passes from one bag to the I

den næste, kan den passere gennem mindst ét porøst medium. the next, it may pass through at least one porous medium. I IN

10 Hvis det biologiske fluidum er det ovenstående lag, f.eks. 10, if the biological fluid is the supernatant layer, for example. I IN

PRP, kan det typisk passere fra opsamlingsposen gennem ét I PRP, it may typically pass from the collection bag through an I

eller flere organer eller én eller flere sammensætninger I or more bodies or one or more compositions in

indeholdende ét eller flere porøse medier - et leucocytfjer- I containing one or more porous media - a leucocytfjer- In

nelsesmedium, et barrieremedium for røde blodlegemer, et 15 porøst medium, der kombinerer barrieren for røde blodlegemer med leucocytfjernelse i ét porøst medium, eller et leucocyt- fjernelsesmedium og et barrieremedium for røde blodlegemer formation medium, a barrier medium for red blood cells, a porous medium 15, which combines the red cell barrier with leucocyte depletion in one porous medium, or a leukocyte removing medium and a barrier medium for red blood cells

i serie. in series. Det ovenstående lag 31 udpresses fra den første I The supernatant layer 31 is expelled from the first in

beholder 11, indtil strømningen standses, typisk ved lukning I container 11 until flow is stopped, typically by closing In

20 af en klemme i ledningen 20, eller automatisk, såfremt sam* I 20 of a clamp in conduit 20, or automatically if the sam * I

mensætningen omfatter et barrieremedium 12 for røde blod- I composition comprises a barrier medium 12 for red blood In

legemer. bodies. Fortrinsvis ledes det ovenstående lag gennem et I Preferably passed the supernatant layer through an I

barrieremedium for røde blodlegemer og dernæst gennem et I barrier medium for red blood cells and then through an I

leucocytfjernelsesmedium. leucocyte depletion. Det ovenstående lag befries dernæst I The supernatant layer is then freed in

25 for leucocyter efter passage gennem leucucytf jemelsesmediet. 25 for leucocytes after passing through leucucytf jemelsesmediet. I IN

Yderligere behandling kan om ønsket finde sted nedstrøms i I Further treatment can, if desired, take place downstream of I

forhold til leucocytf jemelsesmediet, enten i forbindelse I relative to leucocytf jemelsesmediet, either Compound I

med systemet eller efter at være adskilt fra systemet. with the system or after being separated from the system. I IN

Sedimentlaget 32 i opsamlingsposen 11 kan ledes gennem I The sediment layer 32 in collection bag 11 may be passed through I

30 en leucocytf jernel sessammensætning 17 og ind i en beholder I 30 is a leucocytf jernel sessammensætning 17 and into a container in the

18, f.eks. 18, for example. en satellitpose. a satellite bag. Opsamlingsposen 11, der nu in- I The collection bag 11, now in-I

deholder primært røde blodlegemer, underkastes derpå typisk I deholder primarily red cells, is then subjected to typical I

et trykdifferentiale som ovenfor omtalt til priming af leu- I a pressure differential as mentioned above for priming the leukocyte In

cocytf jernel sesammensætningen 17 og til initiering af strøm- I cocytf jernel phase composition were 17 and for initiating the current I

35 ning. 35 up. I IN

I overensstemmelse med en yderligere udførelsesform I In accordance with a further embodiment, I

59 DK 175916 B1 ji tilvejebringes der en fremgangsmåde, ved hvilken udvinding af forskellige biologiske fluida, der er indesluttet eller tilbageholdt i forskellige elementer af systemet, maksimeres, enten ved at bevirke, at et rumfang gas bag det indesluttede 5 eller tilbageholdte biologiske fluidum trænger væsken gennem disse elementer og ind i den udvalgte beholder, sammensætning eller porøse medium, eller ved at trække det indesluttede eller tilbageholdte fluidum ind i den pågældende beholder, sammensætning eller porøse medium ved hjælp af trykdifferen-10 tialet, f.eks. 59 DK 175916 B1 ji, there is provided a method, in which the recovery of various biological fluids trapped or retained in various elements of the system is maximized, either by causing a volume of gas behind the entrapped 5 or retained biological fluid penetrates the liquid through those elements and into the selected container, composition or porous medium, or by drawing the trapped or retained fluid into the respective container, composition or porous medium by pressure difference potential is 10, for example. ved tyngdekraftens hjælp, ved hjælp af en trykmanchet, sugning eller lignende. by gravity, by means of a pressure cuff, suction, or the like. Herved fås der en mere fuldstændig tømning af beholderen, sammensætningen eller det porøse medium. This results in a more complete emptying of the container, the composition or the porous medium. Når først beholderen er fuldstændig tømt, standses strømningen automatisk. Once the container is completely emptied, the flow is stopped automatically.

15 For at den her omhandlede opfindelse kan forstås fuldt ud, angives de følgende eksempler, der vedrører anvendelsen af opfindelsen. 15 In order that the present invention may be fully understood, the following examples are related to the use of the invention.

Eksempler 20 Eksempel 1 Examples 20 Example 1

Det behandlingssystem for biologisk fluidum, der anvendes i dette første eksempel, omfatter en blodopsamlingspose, særskilte PRP- og PRC-leucocytfjernelsesorganer, samt særskilte PRP- og PRC-satellitposer. The processing system for the biological fluid used in the first example includes a blood collection bag, separate PRP and PRC leucocytfjernelsesorganer, as well as separate PRP and PRC satellite bags. Desuden hindrer 25 et barrieremedium for røde blodlegemer mellem opsamlingsposen og PRP-leucocytfjernelsesorganet strømningen af røde blodlegemer ind i PRP-satellitposen. In addition, 25 prevents a barrier medium for red blood cells between the collection bag and the PRP leucocyte depletion assembly the flow of red blood cells into the PRP satellite bag.

Barrieresammensætningen for røde blodlegemer omfatter et porøst medium til blokering af strømning ved kontakt med 30 røde blodlegemer, når PRP passerer fra opsamlingsposen. The barrier composition for red blood cells comprises a porous medium for blocking flow upon contact 30 with red blood cells when the PRP passes from the collecting bag. Barrieresammensætningen for røde blodlegemer er for-formet ud fra PBT-fibre med en gennemsnitlig diameter på 2,6 μπη, hvilke fibre er blevet overflademodificeret i overensstemmelse med de metoder, der er beskrevet i US patent skrift 35 nr. 4.880.548, under anvendelse af hydroxyethylmethacrylat og methacrylsyre i et monomerforhold på 0,35:1 til opnåelse The barrier composition of red blood cells is pre-molded from PBT fibers having an average diameter of 2.6 μπη, which fibers have been surface modified in accordance with the methods described in U.S. Patent 35 no. 4,880,548, using of hydroxyethyl methacrylate and methacrylic acid in a monomer ratio of 0.35: 1 to give

60 I In 60

DK 175916 B1 I In DK 175916 B1

af en CWST-værdi på 95 dyn/cm og et zeta-potentiale på I a CWST of 95 dynes / cm and a zeta potential of In

-11,4 millivolt. -11.4 millivolts. Den effektive diameter af det porøse element I The effective diameter of the porous element in

er 2,31 cm, hvilket giver et filterareal på 4,2 cm^, tykkel- I is 2.31 cm, resulting in a filter area of ​​4.2 cm ^, the thickness I

sen er 0,051 cm, hulrumsrumfanget er 75% (massefylde 0,34 I late is 0.051 cm, voids volume was 75% (specific gravity 0.34 In

5 g/cm3), og fiberoverfladearealet er 0,08 . 5 g / cm 3), and fiber surface area is 0.08. I IN

Det rumfang PRP, der tilbageholdes i huset, er mindre I The volume of PRP detained in the house, unless you

end 0,4 cm3, hvilket repræsenterer et tab af PRP på grund I than 0.4 cm 3, representing a loss of PRP due to I

af tilbageholdelse på mindre end 0,2%. of retention of less than 0.2%. Strømningen standser I The flow stops in

brat, når de røde. abruptly when the red. blodlegemer når opstrøms-overfladen af I blood cells when the upstream surface of the In

10 barrieresammensætningen for de røde blodlegemer, og der er I 10 the barrier composition of the red blood cells, and which are in

ikke nogen synlige tegn på røde blodlegemer eller hæmoglobin I no visible evidence of red cells or hemoglobin in

nedstrøms. downstream. I IN

PRP-leucocytf j ernel sessammensætningen indeholdende I PRP-leucocytf j ernel sessammensætningen containing I

et porøst medium til fjernelse af leucocyter fra PRP, efter I a porous medium for depleting leucocytes from PRP after I

15 PRP har passeret gennem barrieresammensætningen for røde I PRP 15 has passed through the barrier composition of red I

blodlegemer, er beskrevet i US patentskrift nr. 4.880.548. blood cells, are described in U.S. Pat. No. 4,880,548. I IN

På lignende måde er PRC-leucocytfjernelsessammensætningen, I Similarly, the PRC leucocyte depletion assembly, In

der indeholder et porøst medium til fjernelse af leucocyter I containing a porous medium for depleting leucocytes In

fra enheden af PRC, beskrevet i US patentskrift nr. I from the unit of PRC is described in U.S. Pat. No. I

20 4.925.572. 20 4,925,572. I eksemplet anvendes en enkelt enhed af helblod, I In the example, a single unit of whole blood, In

der er givet af en frivillig donor. that is given by a volunteer donor. Enheden af blod opsamles I The unit of blood is collected into

i en opsamlingspose, der i forvejen er fyldt med 63 ml CPDA- I in a collection bag, which is already filled with 63 ml CPDA- In

ant ikoagula ti onsmiddel. ant ikoagula ten oxidating agent. Det opsamlede blod underkastes "soft- I The collected blood is subjected to "Soft In

spin"-centrifugering i overensstemmelse med gængs blodbank- I spin "centrifugation in accordance with current blodbank- In

25 praksis. 25 practice. Opsamlingsposen overføres, idet man drager omsorg I The collection bag is transferred, with care In

for ikke at forstyrre dens indhold, til en plasmaekstraktor, I to avoid disturbing its contents, to a plasma extractor, In

der er fjederpåvirket til udvikling af et tryk på ca. which is spring biased to develop a pressure of about 90 mm I 90 mm In

Hg. Hg. I IN

Trykket fra ekspressoren driver PRP fra opsamlingspo- I The pressure from the expressor drives the PRP from opsamlingspo- In

30 sen gennem barrieresammensætningen for røde blodlegemer, I 30 late through the barrier composition of red blood cells, In

PRP-filterorganet (hvor det gøres leucocytfattigt) og dernæst I PRP filter means (in order to make leucocytfattigt), and then in

til satellitposen. to satellite bag. Når PRP træder ud af opsamlingsposen, I When PRP exited the collection bag, I

stiger grænsefladen mellem PRC og PRP. increase the interface between the PRC and PRP. Når de røde blod- I When the red blood I

legemer (der er til stede i den førende kant af PRC-laget) I elements (which are present in the leading edge of the PRC layer) In

35 kommer i kontakt med barrieresammensætningen for røde blod- I 35 comes in contact with the barrier composition of red blood In

legemer, afsluttes strømningen automatisk og uden overvåg- I bodies, the flow is terminated automatically and without monitoring I

DK 175916 B1 61 ning. DK 175916 B1 61 up.

PRC, der bliver tilbage i opsamlingsposen, behandles også. PRC remaining in the collection bag, are also addressed. Opsamlingsposen ophænges og sammentrykkes derefter ! The collection bag is suspended and then compressed! til priming af PRC-leucocytf jernelsesfilteret, og PRC befries ! to prime the PRC-leucocytf EMOVING the filter, and the PRC is freed! 5 for leucocyter. 5 of leucocytes. Når den ophængte opsamlingspose er tom, standser processen automatisk. When the suspended collection bag is empty, the process stops automatically. Det fremkomne produkt af røde blodlegemer, der nu er befriet for leucocyter, opsamles dernæst i satellitposen og er tilgængeligt for transfusion til en patient efter behov. The resulting product of red blood cells, now freed of leukocytes, are then collected in the satellite bag, and is available for transfusion into a patient as required.

10 PRP, der tidligere er opsamlet i satellitposen, be handles derpå under anvendelse af normale blodbankprocedurer, dvs. 10 PRP previously collected in the satellite bag, is then be traded using normal blood bank procedures, i.e. "hard-spin"-centrifugering, til fremstilling af PC og plasma. "Hard-spin" centrifugation, to produce PC and plasma.

15 Eksempel 2 Example 15 2

Helblod opsamles i et Adsol®-donorsæt og behandles under standardbetingelser til opnåelse af én enhed af PRP. Whole blood is collected in a Adsol®-donor set and is treated under standard conditions to give a unit of PRP.

PRP filtreres derpå til fjernelse af leucocyter under anvendelse af et filterorgan som beskrevet i US patentskrift nr. PRP was then filtered to remove leucocytes using a filter means as described in U.S. Pat.

20 4.880.548. 20 4,880,548. Fjernelseseffektiviteten er større end 99,9%. The removal efficiency greater than 99.9%.

Den filtrerede PRP-enhed anbringes derpå i en trykmanchet, der udsættes for et tryk på 300 mm Hg. The filtered PRP unit was then placed in a pressure cuff which is subjected to a pressure of 300 mm Hg. Røret, der træder ud af posen (klemmelukket på dette punkt) forbindes til indløbet af et adskillelsesorgan som vist i fig. The tubing exiting the bag (clamp closed at this point) is connected to the inlet of a separator as shown in Fig. 5, 6 25 og 9. En mikroporøs polyamidmembran med en porestørrelse på 0,65 μτη anvendes som separationsmediet i organet. 5, 6, 25, and 9. A microporous polyamide membrane having a pore size of 0.65 μτη used as the separation medium in the organ. Arealet af membranen er ca. The area of ​​the membrane is ca. 17,4 cm2. 17.4 cm 2. Dybden af de første fluidum-strømningsbanekanaler formindskes ca. The depth of the first fluid flow path channels decreased ca. 0,03 cm nær ved indløbet til ca. 0.03 cm near the inlet to about 0,01 cm nær ved udløbet. 0.01 cm near the outlet. Dybden af de andre 30 fluidumstrømningsbanekanaler er ca. The depth of the other fluid flow path channels 30 is about 0,025 cm. 0.025 cm. Udløbsåbningerne for organet forbindes til rør, der tillader rumfanget af fluidum, der træder ud af organet, at måles og blive tilbageholdt til analyse. The outlet openings of the body are connected to tubes that allow the volume of fluid exiting the body to be measured and be retained for analysis.

Afprøvningen af den foreliggende opfindelse påbegyndes 35 ved åbning af klemmen, hvorved man tillader PRP at træde ind i organet. The testing of the present invention is started 35 by opening of the clip, thereby allowing PRP to enter the device. Klar væske (plasma) iagttages at træde ud af Clear fluid (plasma) was observed to come out of

62 I 62

DK 175916 B1 I In DK 175916 B1

én åbning, og uklar væske (blodpladekoncentrat) træder ud I an opening and turbid fluid (platelet concentrate) exits in

af den anden åbning. of the second opening. Varigheden af forsøget er 42 minutter, The duration of the test is 42 minutes,

i løbet af hvilket tidsrum der opsamles 154 ml plasma og 32 I during which time 154 mL is collected plasma and 32 of

ml blodpladekoncentrat. ml of platelet concentrate. Koncentrationen af blodplader i I The concentration of platelets in the I

5 plasmaet findes at være 1,2 x 104 pr. 5 the plasma was found to be 1.2 x 104 per. μΐ, medens koncentra- I μΐ, while the concentration in

tionen af blodplader i blodpladekoncentrationen findes at I deletion of platelets in the platelet concentration was found to I

være 1,43 x 106 pr. be 1.43 x 106 per. μΐ. μΐ. I IN

De ovenfor angivne resultater viser, at blodplader I The above results indicate that platelets in

kan koncentreres til et nyttigt niveau, og at plasma kan I may be concentrated to a useful level and plasma can

10 udvindes på en rimelig tid ved hjælp af et organ som her I 10 is recovered in a reasonable time by means of a body which here I

omhandlet. meaning. I IN

Eksempel 3 I Example 3

Helblod opsamles og behandles til blodbestanddele I Whole blood is collected and processed to blood components I

15 som i eksempel 2, og der sammenlignes med det resultat, der I 15 as in Example 2, and compared to the result which I

opnås ved konventionel behandling. achieved by conventional therapy. Resultaterne til sammen- II The results for comparative II

ligning af blodbestanddel-rumfangene og deres respektive I Equation of the blood component-volumes and their respective I

leucocytantal er angivet i den følgende tabel I, der viser I White blood cell count are given in the following Table I which shows the I

den forøgede effektivitet af leucocytfjemelse i forhold I the increased efficiency of leucocytfjemelse relative In

2 0 til de konventionelle metoder. 2 0 to the conventional methods. Tabel I viser også det for- I Table I also shows the front I

øgede udbytte af plasma og tilsvarende formindskede udbytte I increased yield of plasma and corresponding decreased yield in

af PRC, hvilket er et resultat af anvendelsen af den fore- I of PRC, which is a result of the application of the IN PREVIOUS

liggende opfindelse. invention. I IN

Tabel I table I

63 DK 175916 B1 63 DK 175916 B1

Konventionel Ifølge opfindelsen Conventional According to the invention

Helblod 5 rumfang (cm3) 450 - 500 450 - 500 WBC-helblod 2 x 109 2 x 109 PC-rumfang {cm3) 50 - 65 50 - 65 WBC-PC =1 x 108 =1 x 105 P1asma-rumfang 10 (cm3) 165 - 215 170 - 220 WBC-plasma <108 <10® PRC-rumfang (cm3)* 335 320 WBC-PRC* 2 x 109 1 x 106 15 _ Whole blood 5 volumes (cm 3) 450 - 500450-500 WBC-whole blood 2 x 109 2 x 109 PC volume {cm 3) 50 to 65 50 to 65 WBC-PC = 1 x 108 = 1 x 105 P1asma-volume 10 (cm 3 ) 165 - 215170-220 WBC-plasma <108 <10® PRC-volume (cm 3) * 335 320 WBC-PRC * 2 x 109 1 x 106 15 _

* med Adsol® I * With Adsol® In

Eksempel 4-8 example 4-8

De blodopsamlingssæt, der anvendes til gennemførelse 20 af eksemplerne, er i generel overensstemmelse med fig. The blood collection sets used for the implementation of the Examples 20, is in general accordance with Fig. 1, 1

uden det valgfri barrieremedium for røde blodlegemer, og I without the optional barrier medium for red blood cells, and I

proceduren er som tidligere beskrevet, idet der anvendes et apparat svarende til fig. the procedure is as previously described, using an apparatus similar to FIG. 4 til det første centrifugeringstrin. 4 for the first centrifuging step.

25 Det porøse medium til fjernelse af leucocyter fra 25 The porous medium for depleting leucocytes from

PRP er for-formet til et cylindrisk filterelement med en diameter på 2,5 cm og en tykkelse på 0,33 cm, idet der anvendes PBT-fibre med en gennemsnitlig diameter på 2,6 μιη og med en massefylde på 1,38 g/cm3, hvilke fibre er blevet 30 overflademodificeret i overensstemmelse med de metoder, der er beskrevet i US patentskrift nr. 4.880.548, under anvendelse af en blanding af hydroxyethylmethacrylat og methacryl-syremonomere i et vægtforhold på 0,3:1. PRP is pre-formed into a cylindrical filter element having a diameter of 2.5 cm and a thickness of 0.33 cm, using PBT fibers with a mean diameter of 2.6 μιη and having a density of 1.38 g of / cm 3, the fibers 30 have been surface modified in accordance with the methods described in U.S. Pat. No. 4,880,548, using a mixture of hydroxyethyl methacrylate and methacrylic acid monomers in a weight ratio of 0.3: 1. Det porøse medium har en CWST-værdi på 95 dyn/cm og et zeta-potentiale på I The porous medium has a CWST of 95 dynes / cm and a zeta potential of In

35 -11,4 millivolt ved plasmaets pH-værdi (7,3). 35 -11.4 millivolts at the pH of plasma (7.3). Fiberoverflade arealet er 0,52 m2, og hulrumsrumfanget er 80%. Fiber surface area was 0.52 m2, and voids volume was 80%.

I DK 175916 B1 I In DK 175916 B1 In

I 64 I In 64

I Det porøse medium til fjernelse af leucocyter fra I In the porous medium for depleting leucocytes from the I

H PRC beregnes, i overensstemmelse med de i det foregående I H PRC is calculated, in accordance with the above in

angivne ligninger (3) og (4), til opnåelse af en leucocyt- I indicated equations (3) and (4), to obtain a leukocyte In

fjernelseseffektivitet, der er bedre end log 3 (dvs. >99,9%'s I removal efficiency of better than log 3 (i.e.> 99.9% strength I

5 formindskelse af leucocytindholdet) . 5 reduction of leucocyte content). Dette opnås ved anven- I This is achieved by application in

delse af 3,4 g PBT-fiber med en diameter på 2,6 μτη, ca. APPROVAL 3.4 g of the PBT fiber with a diameter of 2.6 μτη, ca. 13% I 13%

mere fiber end krævet ifølge ligningerne (3) og (4), og til I more fiber than called for according to the equations (3) and (4), and to the I

yderligere forøgelse af leucocytfjernelseseffektiviteten I further increase in leucocytfjernelseseffektiviteten

formindskes hulrumsrumfanget til 81%. the void volume is reduced to 81%. Disse ændringer bringer I These changes bring in

10 effektiviteten op på mere end log 4, dvs. 10 efficiency to more than log 4, ie op mere end 99,99%. up more than 99.99%. I IN

Når PRC udpresses gennem dette filtermedium indeholdt i et I When the PRC was squeezed out through this filter medium contained in an I

hus med en diameter på 6,4 cm, opnås der strømningstider i I housing having a diameter of 6.4 cm, there is obtained the flow times of I

I det ønskede område fra 10 til 40 minutter ved et påsat tryk I In the desired range of 10 to 40 minutes at an applied pressure in

på 90 mm Hg. of 90 mm Hg. Fiberoverfladerne er blevet modificeret på den I The fiber surfaces have been modified in the In

15 måde, der er beskrevet i US patentskrift nr. 4.925.572, I 15 manner to that described in U.S. Pat. No. 4,925,572, In

idet der anvendes en blanding af hydroxyethylmethacrylat og I using a mixture of hydroxyethyl methacrylate and I

I methylmethacrylat i et vægtforhold på 0,27:1. In methyl methacrylate in a weight ratio of 0.27: 1st Det porøse I In the porous

medium har en CWST-værdi på 66 dyn/cm. medium has a CWST of 66 dynes / cm. I IN

Det ovenfor beskrevne PRC-porøse medium har foran I The above-described PRC porous medium has In front of

20 sig anbragt et for-filter bestående af fem lag PBT-smel- I 20 disposed at a pre-filter consisting of five layers of PBT melt I

teblæst væv, der er oplagt i den i det følgende angivne I teblæst tissue which is stored in the hereinafter indicated I

orden til en total tykkelse på 0,25 cm: I order to a total thickness of 0.25 cm: In

Vægt Fiberdiameter I Weight Fiber Diameter In

I 2 5 Kvalitet mq/cm^ um _ CWST I In 2 5 Quality mq / cm ^ um _ CWST In

I 2,0-0,6 0,002 12 50 I In 2.0 to 0.6 0.002 12 50 In

I 2,0-1,0 0,002 9 50 I In 2.0 to 1.0 50 0.002 9 I

I 2,5-3,5 0,003 4,5 66 I In 2.5-3.5 0.003 4.5 66

I 5,6-7,1 0,006 3,0 66 I In 5.6 to 7.1 0.006 3.0 66

I 30 5,2-10,3 0,006 2,6 66 . I 30 from 5.2 to 10.3 0.006 2.6 66 thereof. I IN

II hvert af eksemplerne anvendes en enkelt enhed af I II each of the examples used a single unit of I

I blod afgivet af en frivillig donor. In the blood delivered by a volunteer donor. Enheden af blod opsamles I The unit of blood is collected into

I i et blodopsamlingssæt udformet som vist i fig. In a blood collection in accordance with the illustration in Fig. l (uden det I L (without the IN

35 valgfri barrieremedium for røde blodlegemer), idet opsam- I 35 optional barrier medium for red blood cells), the collecting I

I lingsposen i sættet i forvejen er fyldt med 63 ml CPDA-an- I In the treatment bag in the set of pre-filled with 63 ml of CPDA-I AN-

DK 175916 B1 65 tikoagulationsmiddel. DK 175 916 B1 65 tikoagulationsmiddel. Det rumfang blod, der opsamles fra de forskellige donorer, er vist i søjle 1 i den følgende tabel II. The volume of blood that is collected from the various donors is shown in Column 1 of Table II. Opsamlingssættet anbringes i centrifugekurven ifølge fig. The collection kit is placed in the centrifuge basket according to FIG. 4 i overensstemmelse med almindelig blodbankpraksis, 5 men med den undtagelse, at PRC-filteret samles med støtten, der igen er anbragt på den øvre del af centrifugekurven, hvorved man sikrer PRC-filteret udenpå og over centrifugekurven . 4 in accordance with normal blood bank practice, 5 except that the PRC filter assembly with the support, which in turn is disposed on the upper portion of the centrifuge bucket, thus ensuring the PRC filter outside and above the centrifuge bucket.

Centrifugen roteres dernæst ved en hastighed, der 10 udvikler 2280 G <ved bunden af kurven) i 3 minutter, hvilket er tilstrækkeligt til at bevirke, at de røde blodlegemer sedimenterer i den nedre del af opsamlingsposen. The centrifuge is then rotated at a speed which develops 10 2280 G <the bottom of the basket) for 3 minutes, which is sufficient to cause the red blood cells sediment in the lower portion of the receiving bag. Støtten fjernes derpå, og opsamlingsposen overføres, idet man drager omsorg for ikke at forstyrre dens indhold, til en plasma-15 ekstraktor, der er fjederpåvirket til udvikling af tryk på ca. The support is then removed and the collection bag is transferred, with care to avoid disturbing its contents, to a plasma extractor 15, which is spring biased to develop pressure of about 90 mm Hg. 90 mm Hg. Brydning af forseglingen, der forbinder opsamlingsposen og PRP-filteret, og dernæst brydning af forseglingen, der forbinder PRP-filteret og satellitposen, tillader det PRP-ovenstående lag at strømme fra opsamlingsposen gennem 20 PRP-filteret ind i satellitposen. Breaking of the seal connecting the collection bag and the PRP filter and then breaking the seal connecting the PRP filter to the satellite bag, permitting the PRP supernatant layer to flow from the collection bag through 20 the PRP filter into the satellite bag. Efterhånden som PRP træder ud, stiger grænsefladen mellem PRC og PRP i opsamlingsposen, idet strømmen fortsætter i ca. As the PRP exited, increasing the interface between the PRC and PRP in the collection bag, the flow continues for about 10 til 20 minutter, indtil alt PRP er passeret gennem PRP-filteret, på hvilket tidspunkt strømningen standser brat og automatisk, når den førende 25 kant at PRC-laget når PRP-filteret. 10 to 20 minutes until all of the PRP is passed through the PRP filter, at which point the flow stops abruptly and automatically as the leading edge 25 to the PRC layer when the PRP filter. Røret sammenklemmes derpå stødende op til opsamlingsposen og stødende op til satellitposen, og røret mellem de to klemmer og PRP-filteret opskæres. The tube is then clamped adjacent to the collection bag, and adjacent to the satellite bag, and the tubing between the two clamps and the PRP filter was cut. PRP-opsamlet i satellitposen behandles derpå under anvendelse af normale blodbankprocedurer til dannelse af 30 leucocytfattig PC og plasma. PRP collected in the satellite bag was then processed using normal blood bank procedures to produce leucocyte-depleted PC 30 and plasma. Rumfangene af PC og plasma er vist i tabel II sammen med antallet af resterende leucocyter i PC. The volumes of PC and plasma are shown in Table II along with the number of residual leucocytes in the PC.

Opsamlingsposen, der nu kun indeholder de sedimenterede røde blodlegemer, fjernes fra plasmaekstraktoren, og 35 100 ml AS3-næringsopløsning, der er blevet anbragt i forvejen i den anden satellitpose, overføres i opsamlingsposen gennem L._ ...___ The collection bag, now containing only the sedimented red blood cells are removed from the plasma extractor, and 35 100 ml of AS3 nutrient solution, which has been arranged in advance in the other satellite bag, are transferred into the collection bag through L._ ...___

DK 175916 B1 I In DK 175916 B1

PCR-filteret· Indholdet af opsamlingsposen sammenblandes I PCR filter · The contents of the collection bag mixed in

derpå grundigt. then thoroughly. Med et tryk på ca. With a pressure of about 120 mm Hg påsat ved tyn- I 120 mm Hg applied by thinner I

gdekraftens hjælp gøres PRC i opsamlingsposen derpå leuco- I gdekraftens done using PRC in the collection bag is then leuco In

cytfattig ved at lede den gennem PRC-filteret til satellit- I cytfattig by passing it through the PRC filter to the satellite in

5 posen. 5 the bag. PRC er herefter tilgængelig til transfusion i en I PRC is then available for transfusion into an I

patient efter behov. patient as needed. Rumfanget, hæmatokrit-værdier og antal- I The volume, hematocrits and the number I

let af resterende leucocyter i PRC er angivet i tabel II. easy of leucocytes residual in the PRC are listed in Table II. I IN

De leucocyt-værdier, der er angivet i tabellen, af- I The leucocyte values ​​indicated in the table, depreciation In

spejler følsomheden af de metoder, der anvendes til bestem- I reflects the sensitivity of the methods used to provi- In

10 melse af antallet af resterende leucocyter i PRC- og PC- I 10 laws of the number of leucocytes residual in the PRC and PC-I

udstrømningerne. emanations. Der påvises faktisk ingen leucocyter i de I They show virtually no leucocytes in the In

for leucocyter befriede udstrømmende fluida i nogen af ek- I the liberated leucocytes flowing fluids in any of ex- In

semplerne. semplerne. Parallele forsøg under anvendelse af mere følsom- H Parallel experiments using more sensitivity H

me, men mere besværlige bestemmelsesmetoder viser, at leuco- I ME, but more laborious methods of determination shows that the leuco In

15 cytfjernelseseffektiviteter er ca. Is about 15 cytfjernelseseffektiviteter 10 til 100 gange bedre I 10 to 100 times better in

end angivet ved de data, der fremgår af tabellen. than indicated by the data shown in the table. I IN

DK 175916 B1 67 DK 175916 B1 67

Tabel II table II

Test 1 Test 2 Test 3 Test 4 Test 5 Test 1 Test 2 Test 3 Test 4 Test 5

Helblod opsamlet [ml) 407 387 399 410 410 5 Helblod-Hct (%) 45 42,5 40 41 38,5 PRP-filtreringstid (min.) 16 11 14 15 19 PRP-rumfang (ml) 211 173 196 177 232 10 PC-rumfang (ml) 47 52 49 69 61 Whole blood was collected [mL) 407 387 399 410 410 whole blood 5-Hct (%) 45 42.5 40 41 38.5 PRP filtration time (min.) 16 11 14 15 19 PRP volume (ml) 211 173 196 177 232 10 PC volume (ml) 47 52 49 69 61

Rest-WBC-PC* <l,0xl05 <l,lxl05 <-1,1x105 <l,5xl05 <l,3xl05 PRC-filtrerings- tid (min.) 15 18 11 11 12 15 PRC-rumfang (ml) 285 318 301 306 288 PRC-Hct (%) 64,5 67 51 52,5 60,5 Residual WBC-PC * <l, 0xl05 <l, lxl05 <-1,1x105 <l, 5xl05 <l, 3xl05 PRC-filtration time (min.) 15 18 11 11 12 15 PRC-volume (ml) 285 318 301 306 288 PRC Hct (%) 64.5 67 52.5 51 60.5

Rest-WBC-PRC* <7,3xl06 <8,0xl06 <7,5xl06 <7,7xl06 <7,2xl06 * pr. Residual WBC-PRC * <7,3xl06 <8,0xl06 <7,5xl06 <7,7xl06 <7,2xl06 * per. enhed 20 unit 20

Claims (33)

68 I DK 175916 B1 I PATENTKRAV. 68 In DK 175 916 B1 in claim. I IN
1. Behandlingssystem for et biologisk fluidum af den I art, der omfatter en første beholder (11) , en anden beholder I (41) og en tredie beholder (18), hvor den første beholder I 5 (11) står i fluid forbindelse med den tredie beholder (18), I idet et porøst medium (17) er indskudt mellem den første I beholder (11) og den tredie beholder (18), hvor det porøse I medium (17) omfatter et leucocytfjernelsesmedium, og den I anden beholder (41) står i fluid forbindelse med den første I 10 beholder (11), kendetegnet ved, at et yderligere I porøst medium (12, 13) er indskudt mellem den første beholder I (11) og den anden beholder (41) i et lukket system, idet I det yderligere porøse medium (12, 13) omfatter et leucocyt- I fjernelsesmedium eller et kombineret leucocytfjernelses- og I 15 barrieremedium for røde blodlegemer. 1. Coating system for a biological fluid of the I type comprising a first container (11), In a second container (41) and a third container (18), wherein the first container I 5 (11) being in fluid communication with the third container (18), in being a porous medium (17) is interposed between the first in the container (11) and the third container (18), wherein the porous L of medium (17) comprising a leucocyte depletion medium, and in the second container (41) is in fluid communication with the first in the 10 container (11), characterized in that a further in the porous medium (12, 13) is interposed between the first container I (11) and the second container (41) in a closed system, as In the further porous medium (12, 13) comprises a leukocyte removal medium or in a combined leucocytfjernelses- and 15 In the barrier medium for red blood cells. I IN
2. System ifølge krav 1, kendetegnet ved, I at det porøse medium (17) og det yderligere porøse medium I (12, 13) omfatter fibre. 2. The system of claim 1, characterized in that in the porous medium (17) and the further porous medium I (12, 13) comprises fibers. I IN
3. System ifølge krav 2, kendetegnet ved, I 20 at det porøse medium (17) og det yderligere porøse medium I (12, 13) indeholder fibre, der er blevet modificeret ved I udsættelse for en monomer indeholdende en polymeriserbar I gruppe og en hydroxylholdig gruppe . 3. The system of claim 2, characterized in that in 20 to the porous medium (17) and the further porous medium I (12, 13) contains fibers that have been modified by in exposure to a monomer comprising a polymerizable group and an In hydroxyl-containing group. I IN
4. System ifølge krav 3, kendetegnet ved, I 25 at fibrene i det første porøse medium (17) og/eller det yder- I ligere porøse medium (12, 13) er blevet modificeret med en I blanding af monomerer indeholdende hydroxyethylmethacrylat I og methacrylsyre. 4. The system of claim 3, wherein the I 25 to the fibers of the first porous medium (17) and / or the outer In ligating porous medium (12, 13) has been modified with an I mixture of monomers comprising hydroxyethyl methacrylate I and methacrylic acid. I IN
5. System ifølge krav 4, kendetegnet ved, I 30 at vægtforholdet mellem methacrylsyre og hydroxyethylmeth- I acrylatmonomer i den modificerende blanding ligger mellem I 0,01:1 og 0,5:1. 5. The system of claim 4, wherein the I 30 the weight ratio of methacrylic acid and hydroxyethyl acrylate monomer I in the modifying mixture is between In 0.01: 1 and 0.5: 1st I IN
6. System ifølge ethvert af kravene 1-5,kende- I tegnet ved, at det yderligere porøse medium (12, 13) I 35 er et kombineret leucocytfjernelsesfilter og barrieremedium I for røde blodlegemer og tillader blodplader at passere igen- I 69 DK 175916 B1 nem, indtil røde blodlegemer blokerer mediet. 6. The system of any one of claims 1-5, charac- I characterized in that the further porous medium (12, 13) 35 is a combined leucocytfjernelsesfilter and barrier medium in the red blood cells and permits platelets to pass again-69 In DK 175916 B1 easy until red blood cells block the medium.
7. System ifølge ethvert af kravene 1-6, kendetegnet ved, at det yderligere porøse medium (12, 13) har et zeta-potentiale på fra -3 til -30 millivolt ved en 5 pH-værdi på 7,3. 7. The system of any one of claims 1-6, characterized in that the further porous medium (12, 13) has a zeta potential of from -3 to -30 millivolts at a pH of 5 to 7.3.
8. System ifølge ethvert af kravene 1-7, kendetegnet ved, at det yderligere porøse medium (12, 13) har en CWST-værdi på mere end 70 dyn/cm. 8. The system of any one of claims 1-7, characterized in that the further porous medium (12, 13) has a CWST of greater than 70 dynes / cm.
9. System ifølge ethvert af kravene 1-7, kende-10 tegnet ved, at det porøse medium (17) har en CWST- værdi på mere end 53 dyn/cm. 9. The system of any one of Claims 1-7, characterized-10 characterized in that the porous medium (17) has a CWST- value of greater than 53 dynes / cm. 1 1
10. System ifølge ethvert af kravene 1-9, kendetegnet ved, at det omfatter mindst ét gasindtag (53) . 10. The system of any one of claims 1-9, characterized in that it comprises at least one gas inlet (53).
11. System ifølge ethvert af kravene 1-10, ken detegnet ved, at det omfatter mindst ét gasudtag (54) . 11. The system of any one of claims 1-10, Ken characterized in that it comprises at least one gas outlet (54).
12. Fremgangsmåde til behandling af et biologisk fluidum af den art, der omfatter adskillelse af det biologi - 20 ske fluidum i et overliggende lag og et sedimentlag og passage af sedimentlaget af det biologiske fluidum gennem et porøst medium (17), hvor det porøse medium (17) indeholder et leucocytfjernelsesmedium, kendetegnet ved, at -man leder det overliggende lag af det biologiske fluidum 25 gennem et yderligere porøst medium (12,13) i et lukket system, hvor det yderligere porøse medium (12,13) omfatter et leucocytf jernel sesmedium eller et kombineret leucocytf j emelses- og barrieremedium for røde blodlegemer. 12. A method for treating a biological fluid of the type comprising separating the biology - 20 be fluid into a supernatant layer and a sediment layer and passing the sediment layer of the biological fluid through a porous medium (17), wherein the porous medium (17) contains a leucocyte depletion medium, characterized in that the conductor -Man the surface layer of the biological fluid 25 through a further porous medium (12,13) ​​in a closed system, the further porous medium (12,13) ​​comprises a leucocytf jernel sesmedium or a combined leucocytf emelses- j and the barrier medium for red blood cells.
13. Fremgangsmåde ifølge krav 12, kendete g-30 net ved, at der indføres gas gennem et gasindtag (53). 13. The method of claim 12, kendete G-30 characterized in that the gas is introduced through a gas inlet (53).
14. Fremgangsmåde ifølge ethvert af kravene 12-13, kendetegnet ved, at der uddrives gas gennem et gasudtag (54). 14. A method according to any one of claims 12-13, characterized in that the gas is expelled through a gas outlet (54).
15. Fremgangsmåde ifølge ethvert af kravene 12-14, 35 kendetegnet ved, at passage af det biologiske fluidum gennem det yderligere porøse medium (12, 13) omfatter I DK 175916 B1 IIII passage af det overliggende lag gennem et kombineret leuco- II cytfjernelsesmedium og barrieremedium for røde blodlegemer, I indtil mediet er blokeret. 15. A method according to any one of claims 12 to 14, 35 characterized in that the passage of the biological fluid through the further porous medium (12, 13) comprises In DK 175916 B1 IIII passage of the surface layer through a combined leuco II cytfjernelsesmedium and barrier medium for red blood cells, in until the medium is blocked. I IN
16. Biologisk fluidumbehandlingssystem af den art, I m 5 der omfatter en første beholder (11), en anden beholder . 16. Biological fluid treatment system of the type I 5 m comprising a first container (11), a second container. II (41) og en tredie beholder (18) , hvor den første beholder II . II (41) and a third container (18), wherein the first vessel II. (11) er i fluid forbindelse med den tredie beholder (18) , II idet et porøst medium (17) er indskudt mellem den første II beholder (11) og den tredie beholder (18), hvor det porøse ; (11) is in fluid communication with the third container (18) II as a porous medium (17) is interposed between the first II vessel (11) and the third container (18), wherein the porous; II 10 medium (17) indeholder et leucocytfjernelsesmedium, og den ! II 10 medium (17) comprising a leucocyte depletion, and the! II anden beholder (41) er i fluid forbindelse med den første II beholder (11)»kendetegnet ved, at et barriererne- II dium for røde blodlegemer (12, 13) er indskudt mellem den II første beholder (11) og den anden beholder (41) i et lukket II 15 system. II second container (41) is in fluid communication with the first tank II (11) 'characterized in that a barriererne- II medium for red blood cells (12, 13) is interposed between the first container II (11) and the second container (41) in a closed system 15 II. I IN
17. System ifølge krav 16, kendetegnet II ved, at det porøse medium (17) og barrieremediet for røde II blodlegemer (12, 13) indeholder fibre. 17. The system of claim 16, characterized II in that the porous medium (17) and barrier medium for red blood cells II (12, 13) contains fibers. I IN
18. System ifølge krav 17, kendetegnet II 2 0 ved, at det porøse medium (17) og barrieremediet for røde II blodlegemer (12, 13) indeholder fibre, der er blevet modifi- II ceret ved udsættelse for en monomer indeholdende en polymeri- I serbar gruppe og en hydroxylholdig gruppe. 18. The system of claim 17, characterized II 2 0 in that the porous medium (17) and barrier medium for red blood cells II (12, 13) contains fibers that have been modified II induced by exposure to a monomer containing a polymerization In serbar group and a hydroxyl group. I IN
19. System ifølge krav 18, kendetegnet II 25 ved, at fibrene i det porøse medium (17) og/eller barriererne- II diet for røde blodlegemer (12, 13) er blevet modificeret II med en blanding af monomerer indeholdende hydroxyethylmeth- II acrylat og methacrylsyre. 19. The system of claim 18, characterized II 25 in that the fibers of the porous medium (17) and / or II barriererne- diet of red blood cells (12, 13) has been modified II with a mixture of monomers comprising hydroxyethyl acrylate II and methacrylic acid. I IN
20. System ifølge ethvert af kravene 16-19, ke η- II 30detegnet ved, at barrieremediet for røde blodlegemer II (12, 13) tillader blodplader at passerer igennem, indtil II røde blodlegemer blokerer mediet. 20. The system of any one of claims 16-19, KE η- II 30detegnet in that the barrier medium for red blood cells II (12, 13) allows platelets to pass through until red cells block the II medium. I IN
21. System ifølge ethvert af kravene 16-20, ke η- II detegnet ved, at barrieremediet for røde blodlegemer II 35 (12, 13) har et zeta-potentiale fra -3 til -30 millivolt II ved en pH-værdi på 7,3. 21. The system of any one of claims 16-20, KE η- II characterized in that the barrier medium for red blood cells II 35 (12, 13) has a zeta potential of from -3 to -30 millivolts II at a pH of 7 , third I ί 71 DK 175916 B1 In ί 71 DK 175916 B1
22. System ifølge ethvert af kravene 16-21, kendetegnet ved, at barrieremediet for røde blodlegemer (12,13) har en CWST-værdi på mere end 70 dyn/cm. 22. The system of any one of claims 16-21, characterized in that the barrier medium for red blood cells (12,13) ​​has a CWST of greater than 70 dynes / cm.
23. System iflge ethvert af kravene 16-21, ke n-5 detegnet ved, at det første porøse medium (17) har en CWST-værdi på mere end 53 dyn/cm. 23. System iflge any one of claims 16-21, KE-5 characterized in that the first porous medium (17) has a CWST of greater than 53 dynes / cm.
24. System ifølge ethvert af kravene 1-11 og 16-23, kendetegnet ved, at det biologiske fluidum er et blodprodukt. 24. The system of any one of claims 1-11 and 16-23, characterized in that the biological fluid is a blood product.
25. System ifølge ethvert af kravene 1-11 og 16-24, kendetegnet ved, at systemet er et lukket sterilt system. 25. The system of any one of claims 1-11 and 16-24, characterized in that the system is a closed sterile system.
26. Fremgangsmåde til behandling af et biologisk fluidum af den art, der omfatter adskillelse af det biolo- 15 giske fluidum i et overliggende lag og et sedimentlag og passage af sedimentlaget af det biologiske fluidum gennem et porøst leucocytfjernelsesmedium, kendetegnet ved, at man leder det overliggende lag af det biologiske fluidum gennem et barrieremedium (12,13) for røde blodlegemer 20. et lukket system. 26. A method for treating a biological fluid of the type comprising separating the biologi- 15 cal fluid into a supernatant layer and a sediment layer and passing the sediment layer of the biological fluid through a porous leucocyte depletion medium, characterized in that passing the the surface layer of the biological fluid through a barrier medium (12,13) ​​of red blood cells 20 a closed system.
27. Fremgangsmåde ifølge krav 26, kendetegnet ved, at der indføres af gas gennem et gasindtag (53). 27. A method according to claim 26, characterized in that the introduction of gas through a gas inlet (53).
28. Fremgangsmåde ifølge ethvert af kravene 26-27, kendetegnet ved, at der uddrives af gas gennem 25 et gasudtag (54). 28. A method according to any one of claims 26-27, characterized in that the expelled gas 25 through a gas outlet (54).
29. Fremgangsmåde ifølge ethvert af kravene 26-28, kendetegnet ved, at passage af det biologiske fluidum gennem barrieremediet for røde blodlegemer (12, 13) omfatter passage af det overliggende lag gennem barrierelaget 30 for røde blodlegemer, indtil mediet er blokeret. 29. A method according to any one of claims 26-28, characterized in that the passage of the biological fluid through the barrier medium for red blood cells (12, 13) comprises the passage of the surface layer through the barrier layer 30 of red blood cells until the medium is blocked.
30. Fremgangsmåde ifølge ethvert af kravene 12-15 og 26-29, kendetegnet ved, at det biologiske fluidum er et blodprodukt. 30. A method according to any one of claims 12-15 and 26-29, characterized in that the biological fluid is a blood product.
31. Fremgangsmåde ifølge ethvert af kravene 12-15 og 35 26-30, kendetegnet ved, at man behandler det biologiske fluidum i et lukket sterilt system. 31. A method according to any one of claims 12-15 to 35 26-30, characterized in treating the biological fluid in a closed sterile system.
72 I DK 175916 B1 I 72 In DK 175916 B1 In
32. Fremgangsmåde ifølge ethvert af kravene 12-15 og I 26-31, kendetegnet ved, at man behandler det I biologiske fluidum indenfor ca. 32. A method according to any one of claims 12-15 and 26-31 I, characterized in that the treating in the biological fluid within about 8 timer fra det tidspunkt, I hvor det biologiske fluidum udtages fra et legeme. 8 hours from the time in which the biological fluid taken from a body. I IN
33. Fremgangsmåde til behandling af et biologisk flui- I dum, af den art, der omfatter passage af et biologisk fluidum I fra en første beholder gennem et første porøst medium, hvor I det første porøse medium indeholder et leucocytfjernelses- I medium, og adskillelse af det for leucocyter befriede biolo- I 10 giske fluidum i et overliggende lag (31) og et sedimentlag I (32), kendetegnet ved, at man leder det overlig- I gende lag (31) gennem et andet porøst medium, hvor det andet I porøse medium indeholder mindst ét af et leucocytf jernelses- I medium (13), et barrieremedium for røde blodlegemer (12) og I 15 et kombineret leucocytfjernelses- og barrieremedium for I røde blodlegemer (12). 33. A method for processing a biological fluid in dumb, of the type comprising passing a biological fluid from a first container through a first porous medium, wherein in the first porous medium comprising a leucocytfjernelses- in medium and separating the liberated leucocytes of bio- logical I 10 fluid in an overlying layer (31) and a sediment layer I (32), characterized in that the overlying conductor layer in-taking (31) through a second porous medium, wherein the second In the porous medium containing at least one of a leucocytf jernelses- in medium (13), a barrier medium for red blood cells (12) and in a combined 15 leucocytfjernelses- barrier medium and in red blood cells (12). I IN
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Families Citing this family (155)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5690835A (en) 1991-12-23 1997-11-25 Baxter International Inc. Systems and methods for on line collection of cellular blood components that assure donor comfort
US5549834A (en) 1991-12-23 1996-08-27 Baxter International Inc. Systems and methods for reducing the number of leukocytes in cellular products like platelets harvested for therapeutic purposes
US5344561A (en) * 1989-05-09 1994-09-06 Pall Corporation Device for depletion of the leucocyte content of blood and blood components
US5360545A (en) * 1989-09-12 1994-11-01 Pall Corporation Filter for obtaining platelets
US5316674A (en) * 1989-09-12 1994-05-31 Pall Corporation Device for processing blood for human transfusion
US5152905A (en) * 1989-09-12 1992-10-06 Pall Corporation Method for processing blood for human transfusion
US5258126A (en) * 1989-09-12 1993-11-02 Pall Corporation Method for obtaining platelets
US5266219A (en) * 1989-12-28 1993-11-30 Pall Corporation Device and method for separating plasma from blood
US5126054A (en) * 1990-05-24 1992-06-30 Pall Corporation Venting means
US5863436A (en) * 1990-05-24 1999-01-26 Pall Corporation Venting system
US5302299A (en) * 1990-05-24 1994-04-12 Pall Corporation Biological semi-fluid processing assembly
US5362406A (en) * 1990-07-27 1994-11-08 Pall Corporation Leucocyte depleting filter device and method of use
US5217627A (en) * 1990-11-06 1993-06-08 Pall Corporation System and method for processing biological fluid
WO1994001193A1 (en) * 1992-07-13 1994-01-20 Pall Corporation Automated system and method for processing biological fluid
US5935092A (en) 1990-12-20 1999-08-10 Baxter International Inc. Systems and methods for removing free and entrained contaminants in plasma
US5498336A (en) * 1991-02-22 1996-03-12 Terumo Kabushiki Kaisha Leukocyte-removing filter and leukocyte-removing apparatus furnished therewith
US5672481A (en) * 1991-10-23 1997-09-30 Cellpro, Incorporated Apparatus and method for particle separation in a closed field
CA2074671A1 (en) * 1991-11-04 1993-05-05 Thomas Bormann Device and method for separating plasma from a biological fluid
CA2072378C (en) * 1991-11-21 2000-12-26 Vlado Ivan Matkovich System for processing separate containers of biological fluid
AU4107396A (en) 1992-03-02 1996-06-06 Cerus Corporation Synthetic media for blood components
JPH07507717A (en) * 1992-06-10 1995-08-31
CA2083075A1 (en) * 1992-06-10 1993-12-11 Vlado I. Matkovich System for treating transition zone material
JPH07509153A (en) * 1992-07-13 1995-10-12
GB9218581D0 (en) * 1992-09-02 1992-10-14 Pall Corp Removal of unwanted fluids from processed blood products
DE69324754D1 (en) * 1992-10-07 1999-06-10 Asahi Medical Co Filter and system for the separation of leukocytes
EP0668786A1 (en) * 1992-11-03 1995-08-30 Chronomed, Inc. Methods and procedures for preparing red blood fractions
US5316681A (en) * 1992-11-06 1994-05-31 Baxter International Inc. Method of filtering body fluid using a rinse chamber bag
JP3246620B2 (en) * 1993-02-22 2002-01-15 旭メディカル株式会社 Leukocyte-removing filter support
US5547591A (en) * 1993-06-01 1996-08-20 Asahi Medical Co., Ltd. Method for separating a blood material into blood components by centrifugation, and centrifugal apparatus
GB9311988D0 (en) * 1993-06-10 1993-07-28 Pall Corp Device and method for separating plasma from a blood product
CA2143830C (en) * 1993-07-26 2003-11-25 Richard I. Brown Systems and methods for reducing leukocytes in cellular products
FR2712825B1 (en) * 1993-11-23 1996-02-23 Jouan A method for centrifugal processing of a liquid packed in bags with flexible walls connected to at least one filter.
US5545339A (en) * 1994-02-25 1996-08-13 Pall Corporation Method for processing biological fluid and treating separated component
US5591350A (en) * 1994-04-15 1997-01-07 Pall Corporation Iodine disinfection method using a gaseous iodine treated porous medium
US5547108A (en) * 1994-08-02 1996-08-20 Pall Corporation Expressor
US6045701A (en) * 1994-10-17 2000-04-04 Baxter International Inc. Method of filtering a fluid suspension with a membrane having a particular coating
US6746482B2 (en) 1994-10-17 2004-06-08 Baxter International Inc. Method for producing medical devices and devices so produced
US5972217A (en) * 1994-10-17 1999-10-26 Baxter International Inc. Blood cell separation devices having a membrane with particular coating
US5647985A (en) * 1994-10-17 1997-07-15 Baxter International Inc. Whole blood leukodepletion and platelet filter
US6306454B1 (en) * 1994-10-17 2001-10-23 Baxter International Inc. Method for producing improved medical devices and devices so produced
US5660731A (en) * 1994-11-08 1997-08-26 Pall Corporation Filter for separating photoactive agent
US7169547B2 (en) 1994-12-05 2007-01-30 New York Blood Center, Inc. High concentration white blood cells as a therapeutic product
US5585007A (en) * 1994-12-07 1996-12-17 Plasmaseal Corporation Plasma concentrate and tissue sealant methods and apparatuses for making concentrated plasma and/or tissue sealant
US5728306A (en) * 1994-12-23 1998-03-17 Baxter International Inc. Leukodepletion filter and method for filtering leukocytes from freshly drawn blood
US5630946A (en) * 1995-02-15 1997-05-20 Pall Corporation Method for processing a biological fluid including leukocyte removal in an extracorporeal circuit
US5913768A (en) * 1995-04-18 1999-06-22 Cobe Laboratories, Inc. Particle filter apparatus
US6053856A (en) * 1995-04-18 2000-04-25 Cobe Laboratories Tubing set apparatus and method for separation of fluid components
JP4304264B2 (en) * 1995-04-18 2009-07-29 カリディアンビーシーティ、 インコーポレイテッド Particle separation method and apparatus
US20020115585A1 (en) * 1996-06-07 2002-08-22 Hei Derek J. Method and devices for the removal of psoralens from blood products
US5721024A (en) * 1995-06-07 1998-02-24 Pall Corporation Material for flexible medical products
US6544727B1 (en) 1995-06-07 2003-04-08 Cerus Corporation Methods and devices for the removal of psoralens from blood products
US5759413A (en) * 1995-06-07 1998-06-02 Baxter International Inc. Systems and method for estimating platelet counts using a spleen mobilization function
US6140040A (en) * 1995-10-06 2000-10-31 Advanced Minerals Corporation Method of mechanically separating microparticles suspended in fluids using particulate media
US5865785A (en) * 1996-02-23 1999-02-02 Baxter International Inc. Systems and methods for on line finishing of cellular blood products like platelets harvested for therapeutic purposes
US6190855B1 (en) 1996-10-28 2001-02-20 Baxter International Inc. Systems and methods for removing viral agents from blood
US6168718B1 (en) 1996-11-08 2001-01-02 Pall Corporation Method for purifying blood plasma and apparatus suitable therefor
CA2271440A1 (en) * 1996-12-24 1998-07-02 Barry Wenz Biological fluid processing
US7611831B2 (en) * 1998-01-06 2009-11-03 Cerus Corporation Adsorbing pathogen-inactivating compounds with porous particles immobilized in a matrix
US5954971A (en) * 1997-01-07 1999-09-21 Haemonetics Corporation Pumped-filter blood-processing apparatus and methods
DE19712298C2 (en) 1997-03-24 1999-05-20 Fresenius Ag Device and method for separating blood into blood components
US20010018179A1 (en) 1998-01-06 2001-08-30 Derek J. Hei Batch devices for the reduction of compounds from biological compositions containing cells and methods of use
US20010009756A1 (en) 1998-01-06 2001-07-26 Derek Hei Flow devices for the reduction of compounds from biological compositions and methods of use
US6051146A (en) * 1998-01-20 2000-04-18 Cobe Laboratories, Inc. Methods for separation of particles
WO1999037340A2 (en) * 1998-01-23 1999-07-29 Pall Corporation Biological fluid treatment system
US6669905B1 (en) * 1998-05-21 2003-12-30 Baxter International Inc. Systems and methods for collecting plasma that is free or virtually free of cellular blood species
FR2781681B1 (en) * 1998-07-31 2000-11-24 Maco Pharma Sa Set of pockets in a closed circuit, for collecting, separating and purifying various blood components from a whole blood collection
US6153113A (en) 1999-02-22 2000-11-28 Cobe Laboratories, Inc. Method for using ligands in particle separation
US6334842B1 (en) 1999-03-16 2002-01-01 Gambro, Inc. Centrifugal separation apparatus and method for separating fluid components
US6945411B1 (en) * 1999-03-16 2005-09-20 Pall Corporation Biological fluid filter and system
GB9909630D0 (en) 1999-04-28 1999-06-23 Zeneca Ltd Reactor
US6629919B2 (en) 1999-06-03 2003-10-07 Haemonetics Corporation Core for blood processing apparatus
EP1057534A1 (en) 1999-06-03 2000-12-06 Haemonetics Corporation Centrifugation bowl with filter core
WO2001008546A2 (en) * 1999-07-29 2001-02-08 Baxter International Inc. Sampling tube holder for blood sampling system
US6875191B2 (en) 1999-09-03 2005-04-05 Baxter International Inc. Blood processing systems and methods that alternate flow of blood component and additive solution through an in-line leukofilter
US6524231B1 (en) * 1999-09-03 2003-02-25 Baxter International Inc. Blood separation chamber with constricted interior channel and recessed passage
US7686779B1 (en) 1999-10-01 2010-03-30 Caridian BCT, Inc Extracorporeal blood processing methods and apparatus
US7651474B2 (en) 1999-10-01 2010-01-26 Caridianbct, Inc. Method and apparatus for leukoreduction of red blood cells
US6354986B1 (en) 2000-02-16 2002-03-12 Gambro, Inc. Reverse-flow chamber purging during centrifugal separation
DE60139137D1 (en) * 2000-09-20 2009-08-13 Thermo Fisher Scient Asheville Blood centrifuge tube with replaceable chamber as a holding device for filter
EP1382357B1 (en) * 2001-04-26 2011-10-26 Asahi Kasei Medical Co., Ltd. Blood filtration method
FR2827176B1 (en) * 2001-07-12 2003-12-19 Biolog Process for the reliability of the blood tracabilite levies during mining operations including plasma and red blood cells
US7264608B2 (en) * 2001-12-05 2007-09-04 Fenwal, Inc. Manual processing systems and methods for providing blood components conditioned for pathogen inactivation
AT522237T (en) * 2001-12-10 2011-09-15 Caridianbct Inc A process for reducing the content of leukocytes in a blood cell component of red
US20030173274A1 (en) * 2002-02-01 2003-09-18 Frank Corbin Blood component separation device, system, and method including filtration
WO2003089027A2 (en) * 2002-04-16 2003-10-30 Gambro, Inc. Blood component processing system, apparatus and method
US7992725B2 (en) 2002-05-03 2011-08-09 Biomet Biologics, Llc Buoy suspension fractionation system
US8328024B2 (en) 2007-04-12 2012-12-11 Hanuman, Llc Buoy suspension fractionation system
US20030205538A1 (en) 2002-05-03 2003-11-06 Randel Dorian Methods and apparatus for isolating platelets from blood
US20060278588A1 (en) 2002-05-24 2006-12-14 Woodell-May Jennifer E Apparatus and method for separating and concentrating fluids containing multiple components
US7832566B2 (en) * 2002-05-24 2010-11-16 Biomet Biologics, Llc Method and apparatus for separating and concentrating a component from a multi-component material including macroparticles
US8567609B2 (en) 2006-05-25 2013-10-29 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US7374678B2 (en) * 2002-05-24 2008-05-20 Biomet Biologics, Inc. Apparatus and method for separating and concentrating fluids containing multiple components
US7845499B2 (en) 2002-05-24 2010-12-07 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
AU2003249642A1 (en) * 2002-05-24 2003-12-12 Biomet Manufacturing Corp. Apparatus and method for separating and concentrating fluids containing multiple components
ITTO20020736A1 (en) * 2002-08-21 2004-02-22 Fresenius Hemocare Italia Srl Filter for leukocytes and its use for the impoverishment of the blood produced by leukocytes.
ITTO20020820A1 (en) * 2002-09-20 2004-03-21 Fresenius Hemocare Italia S R L Device and method for separating blood into blood components depleted of leukocytes.
US7297272B2 (en) * 2002-10-24 2007-11-20 Fenwal, Inc. Separation apparatus and method
KR100743483B1 (en) 2002-12-12 2007-07-30 아사히 가세이 가부시키가이샤 Virus-removing bag and virus-removing method using the same
WO2004112477A1 (en) 2003-06-20 2004-12-29 Pall Corporation Processing of platelet-containing biological fluids
US20050124073A1 (en) 2003-12-09 2005-06-09 Entire Interest Fat collection and preparation system and method
US20050137517A1 (en) * 2003-12-19 2005-06-23 Baxter International Inc. Processing systems and methods for providing leukocyte-reduced blood components conditioned for pathogen inactivation
US20050208501A1 (en) 2004-03-16 2005-09-22 Ambion, Inc. Process and reagents for extraction of RNA from fractionated blood leukocytes
CN1972753B (en) 2004-06-22 2010-10-06 科安比司特公司 Bag assembly for the separation of a composite liquid and method of manufacturing it
US7866485B2 (en) 2005-02-07 2011-01-11 Hanuman, Llc Apparatus and method for preparing platelet rich plasma and concentrates thereof
JP4974902B2 (en) * 2005-02-07 2012-07-11 バイオメット バイオロジックス,インコーポレイテッド Method of concentrating apparatus and concentrated platelet-rich plasma
EP1848474B1 (en) * 2005-02-07 2013-06-12 Hanuman LLC Platelet rich plasma concentrate apparatus and method
EP1933899A1 (en) * 2005-10-05 2008-06-25 Gambro BCT, Inc. Method and apparatus for leukoreduction of red blood cells
DE202005015644U1 (en) * 2005-10-06 2007-02-15 Andreas Hettich Gmbh & Co. Kg Centrifuge tube with holder for the blood bag
US8979770B2 (en) * 2006-02-24 2015-03-17 Merck Sharp & Dohme Corp. Extraction and diagnostic fluid devices, systems and methods of use
US8430813B2 (en) * 2006-05-26 2013-04-30 Depuy Spine, Inc. Illuminated surgical access system including a surgical access device and integrated light emitter
US20080147240A1 (en) * 2006-12-19 2008-06-19 Gambro Bct Inc. Apparatus for separating a composite liquid with process control on a centrifuge rotor
US20080156728A1 (en) * 2006-12-29 2008-07-03 Bryan Blickhan Biological fluid filtration systems and methods
EP2570129A3 (en) * 2007-03-07 2013-04-17 JMS Co., Ltd. Serum preparation apparatus
WO2008124678A2 (en) * 2007-04-06 2008-10-16 Fenwal, Inc. Biological fluid filtration systems and methods
WO2008127639A1 (en) * 2007-04-12 2008-10-23 Biomet Biologics, Llc Buoy suspension fractionation system
KR20120093397A (en) * 2007-08-31 2012-08-22 더 리젠츠 오브 더 유니버시티 오브 미시간 Selective cytopheresis devices and related methods thereof
AU2009209515A1 (en) * 2008-01-28 2009-08-06 Milux Holding Sa Blood clot removal device, system, and method
US8075468B2 (en) * 2008-02-27 2011-12-13 Fenwal, Inc. Systems and methods for mid-processing calculation of blood composition
EP2567692B1 (en) 2008-02-27 2016-04-06 Biomet Biologics, LLC Use of a device for obtaining interleukin-1 receptor antagonist rich solutions
US8685258B2 (en) * 2008-02-27 2014-04-01 Fenwal, Inc. Systems and methods for conveying multiple blood components to a recipient
US8337711B2 (en) 2008-02-29 2012-12-25 Biomet Biologics, Llc System and process for separating a material
US8702637B2 (en) 2008-04-14 2014-04-22 Haemonetics Corporation System and method for optimized apheresis draw and return
US8454548B2 (en) * 2008-04-14 2013-06-04 Haemonetics Corporation System and method for plasma reduced platelet collection
US8628489B2 (en) 2008-04-14 2014-01-14 Haemonetics Corporation Three-line apheresis system and method
JP5229665B2 (en) * 2008-05-13 2013-07-03 学校法人立命館 Plasma or serum separation method, and plasma or serum separation devices
US8012077B2 (en) * 2008-05-23 2011-09-06 Biomet Biologics, Llc Blood separating device
FR2934489B1 (en) * 2008-07-31 2011-11-11 Imv Technologies packing bag of a biological substance having suspension apertures has a support device and formed strip of such bags.
US8187475B2 (en) 2009-03-06 2012-05-29 Biomet Biologics, Llc Method and apparatus for producing autologous thrombin
US8834402B2 (en) 2009-03-12 2014-09-16 Haemonetics Corporation System and method for the re-anticoagulation of platelet rich plasma
US8313954B2 (en) 2009-04-03 2012-11-20 Biomet Biologics, Llc All-in-one means of separating blood components
US9011800B2 (en) * 2009-07-16 2015-04-21 Biomet Biologics, Llc Method and apparatus for separating biological materials
US8875893B2 (en) 2010-02-05 2014-11-04 Fenwal, Inc. Medical containers for use in blood collection and processing and medical systems, methods and apparatus for use in blood collection and processing
US8591391B2 (en) 2010-04-12 2013-11-26 Biomet Biologics, Llc Method and apparatus for separating a material
CN103221078B (en) 2010-11-05 2015-09-16 赫摩耐提克斯公司 System and method for automated washed platelets
JP5785713B2 (en) * 2010-12-28 2015-09-30 ファミリーセルバンク株式会社 Leukocyte fraction collection device
US9302042B2 (en) 2010-12-30 2016-04-05 Haemonetics Corporation System and method for collecting platelets and anticipating plasma return
US9642956B2 (en) 2012-08-27 2017-05-09 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
WO2014088882A2 (en) 2012-12-03 2014-06-12 Emd Millipore Corporation Methods and devices used for redundant sterile filtration
US9248446B2 (en) 2013-02-18 2016-02-02 Terumo Bct, Inc. System for blood separation with a separation chamber having an internal gravity valve
US9950035B2 (en) 2013-03-15 2018-04-24 Biomet Biologics, Llc Methods and non-immunogenic compositions for treating inflammatory disorders
US10208095B2 (en) 2013-03-15 2019-02-19 Biomet Manufacturing, Llc Methods for making cytokine compositions from tissues using non-centrifugal methods
US10143725B2 (en) 2013-03-15 2018-12-04 Biomet Biologics, Llc Treatment of pain using protein solutions
US9895418B2 (en) 2013-03-15 2018-02-20 Biomet Biologics, Llc Treatment of peripheral vascular disease using protein solutions
US9943639B2 (en) * 2013-10-28 2018-04-17 Boston Scientific Scimed, Inc. Fluid management system and methods
CN105813663B (en) * 2013-12-13 2017-09-22 旭化成医疗株式会社 The method of leukocyte removal filter material and the leukocyte removal
US9968738B2 (en) 2014-03-24 2018-05-15 Fenwal, Inc. Biological fluid filters with molded frame and methods for making such filters
US10159778B2 (en) 2014-03-24 2018-12-25 Fenwal, Inc. Biological fluid filters having flexible walls and methods for making such filters
US9796166B2 (en) 2014-03-24 2017-10-24 Fenwal, Inc. Flexible biological fluid filters
US9782707B2 (en) 2014-03-24 2017-10-10 Fenwal, Inc. Biological fluid filters having flexible walls and methods for making such filters
CA2951398A1 (en) * 2014-06-24 2015-12-30 Parker-Hannifin Corporation Multiple identification point automated parameter assurance method
US9713810B2 (en) 2015-03-30 2017-07-25 Biomet Biologics, Llc Cell washing plunger using centrifugal force
US9757721B2 (en) 2015-05-11 2017-09-12 Biomet Biologics, Llc Cell washing plunger using centrifugal force
CN105641988B (en) * 2015-12-02 2018-01-30 重庆浪尖渝力科技有限公司 Automatic separation of the biological sample suspension plate assembly apparatus hanging
FR3055556B1 (en) 2016-09-08 2018-10-12 Maco Pharma Sa filtration unit comprising portions dome
FR3055557B1 (en) 2016-09-08 2018-10-12 Maco Pharma Sa filtration unit comprising a curved peripheral edge

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US492362A (en) 1893-02-21 Alois opiioven
US3800947A (en) * 1971-07-16 1974-04-02 P Smith Reagent tube and centrifugally operated solid-liquid separating device
US4111199A (en) * 1977-03-31 1978-09-05 Isaac Djerassi Method of collecting transfusable granulocytes by gravity leukopheresis
GB2018151B (en) * 1978-03-06 1982-12-08 Asahi Chemical Ind Seperation of leukocytes from leukocyte-containing suspension by filtration
EP0026417B1 (en) * 1979-09-22 1983-12-14 Firma Andreas Hettich Centrifuge with system of bloodbag for the separation of blood components
JPS603367B2 (en) * 1979-10-09 1985-01-28 Asahi Chemical Ind
US4322298A (en) * 1981-06-01 1982-03-30 Advanced Blood Component Technology, Inc. Centrifugal cell separator, and method of use thereof
US4416778A (en) * 1981-10-20 1983-11-22 Neocyte, Inc. Means for preparing neocyte enriched blood
US4543084A (en) * 1982-02-09 1985-09-24 Bailey Mary L Blood bag support for centrifugation
US4919823A (en) * 1982-06-04 1990-04-24 Miles Inc. Blood bag system with integral filtering means
US4596657A (en) * 1982-06-04 1986-06-24 Miles Laboratories, Inc. Blood bag system with integral filtering means
US4767541A (en) * 1982-06-04 1988-08-30 Miles Laboratories, Inc. Method of removing platelets and white cells from a red cell concentrate
US4680025A (en) * 1982-08-24 1987-07-14 Baxter Travenol Laboratories, Inc. Blood component collection systems and methods
DE3410286C2 (en) * 1984-03-21 1986-01-23 Fresenius Ag, 6380 Bad Homburg, De
US4753739A (en) * 1986-01-27 1988-06-28 Engineering & Research Associates Blood bag support system
EP0267286B1 (en) * 1986-03-28 1993-05-26 ASAHI MEDICAL Co., Ltd. Filter medium for selectively removing leucocytes
US4915848A (en) * 1986-04-21 1990-04-10 Miles Laboratories, Inc. Red blood cell filtering system
US4855063A (en) * 1986-04-21 1989-08-08 Miles Laboratories, Inc. Red blood cell filtering system
US4810378A (en) * 1986-04-21 1989-03-07 Miles Laboratories, Inc. Red blood cell filtering system
US4714457A (en) * 1986-09-15 1987-12-22 Robert Alterbaum Method and apparatus for use in preparation of fibrinogen from a patient's blood
DE3786641D1 (en) * 1986-10-29 1993-08-26 Asahi Medical Co Unit for recording of blood constituents.
US4923620A (en) * 1987-10-20 1990-05-08 Pall Corporation Device for depletion of the leukocyte content of blood and blood components
US4925572A (en) * 1987-10-20 1990-05-15 Pall Corporation Device and method for depletion of the leukocyte content of blood and blood components
US4909949A (en) * 1987-10-26 1990-03-20 Engineering & Research Associates Bridge for suspending a blood collection bag
US4880548A (en) * 1988-02-17 1989-11-14 Pall Corporation Device and method for separating leucocytes from platelet concentrate
EP0349188B1 (en) * 1988-06-23 1992-09-02 ASAHI MEDICAL Co., Ltd. Method for separating blood into blood components, and blood components separator unit
US4892668A (en) * 1988-10-05 1990-01-09 Engineering & Research Associates, Inc. Blood collection bag support
NL8802888A (en) * 1988-11-23 1990-06-18 Akzo Nv Filter and process for the manufacture of a leucocyte-poor platelet.
US4943287A (en) * 1989-07-17 1990-07-24 Miles Inc. Red blood cell storage system
AT193454T (en) 1989-09-12 2000-06-15 Pall Corp A method and apparatus for treating human blood for transfusion
US4997577A (en) * 1989-12-20 1991-03-05 Baxter International Inc. Systems and methods for removing undesired matter from blood cells
US5089146A (en) * 1990-02-12 1992-02-18 Miles Inc. Pre-storage filtration of platelets
US5092996A (en) * 1991-02-19 1992-03-03 Miles Inc. Blood filtering system

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